Table 2 Annotation and pathogenicity predictions of THRB variants found in our IRD-cohort.

Variant information

Reference (hg19)

chr3-24231564-C-T

chr3-24231565-C-T

Exon/Intron

Intron 5

Exon 5

Nucleotide change

NM_001354712.2: c.283 + 1G > A

NM_001354712.2: c.283G > A

Protein change

NP_001341641.1: p.?

NP_001341641.1: p.Gly95Arg

Type of variant

Splicing

Missense/Splicing

Population Frequencies and Database

gnomAD

Not found

Not found

ClinVar

Pathogenic

Not found

LOVD

Not found

Not found

Splicing predictions

spliceAI_DL

0.98 (at −1 bp)

0.73 (at 0 bp)

spliceAI_DG

0.24 (at −7 bp)

0.08 (at −6 bp)

spliceAI_AL

0.48 (at −261 bp)

0.43 (at −260 bp)

spliceAI_AG

0

0

MaxEntScan_5’ss_cano_WT

9.24

9.24

MaxEntScan_5’ss_cano_MT

1.06

2.93

MaxEntScan_5’ss_aber_WT

0.58

0.58

MaxEntScan_5’ss_aber_MT

0.58

−0.78

SPiP_interpretation

Alteration of the consensus splice site

Alteration of the consensus splice site

SPiP_risk

98.41% [91.47 − 99.96%]

98.41% [91.47 − 99.96%]

dbscSNV_ADA

1

1

dbscSNV_RF

0.94

1

Overall predictions

MPA score

10 (high impact)

10 (high impact)

MPA impact

Clinvar pathogenic

High missense

CADD_phred

34

35

REVEL

–

0.75 (D)

SIFT

–

0.001 (D)

Polyphen 2 HumDiv

–

0.998 (PD)

Polyphen 2 HumVar

–

0.947 (PD)

Fathmm

–

−3.3 (D)

AlphaMissense

–

0.963 (LP)

ClinPred

–

0.961 (D)

Meta SVM

–

0.9848 (D)

Meta LR

–

0.8944 (D)

Mistic

–

0.80 (D)

ACMG classification

P (PS4, PVS1, PM2, PP1, PP3, PP5)

P (PS4, PM1, PM2, PP1, PP2, PP3)

Reference

Fernández-Suárez et al.¹⁶

This study