Variant: NM_000441.1(SLC26A4):c.1363A>T (p.Ile455Phe)

CA132664

43507 (ClinVar)

Gene: SLC26A4

Condition: Pendred syndrome

Inheritance Mode: Autosomal recessive inheritance

UUID: 2b9fd19d-de91-41b2-a416-dc26fa5062e4

HGVS expressions

NM_000441.1:c.1363A>T
NM_000441.1(SLC26A4):c.1363A>T (p.Ile455Phe)
NC_000007.14:g.107694642A>T
CM000669.2:g.107694642A>T
NC_000007.13:g.107335087A>T
CM000669.1:g.107335087A>T
NC_000007.12:g.107122323A>T
NG_008489.1:g.39008A>T
ENST00000265715.7:c.1363A>T
ENST00000460748.1:n.466A>T
ENST00000477350.5:n.210A>T
ENST00000480841.5:n.212A>T
ENST00000497446.5:n.378A>T

Benign

• Met criteria codes: BA1 PP3

• Not Met criteria codes: PS1 PM5 PM1

Expert Panel

Hearing Loss VCEP

Criteria Specification Information

Evidence submitted by expert panel

Hearing Loss VCEP

The filtering allele frequency of the p.Ile455Phe variant in the SLC26A4 gene is 3% (981/30778) of South Asian chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org; calculated by using inverse allele frequency at https://www.cardiodb.org/allelefrequencyapp/), which is a high frequency that is consistent with benign classification based on thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss variants (BA1).

Met criteria codes

• BA1: BS1. Allele frequency is greater than 0.3 %, meets criteria based on gnomAD, ExAC and 1000 genomes. - ANDREA: I think this meets BA1 because the filtering allele frequency is 2.9% in ExAC. Changed to BA1.
• PP3: ILE is conserved through zebrafish. Conflicting lines of computational evidence but meets criteria as REVEL score is 0.89 which is greater or equal to criteria of 0.7.

Not Met criteria codes

• PS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM5: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Approved on: 2018-09-28

Published on: 2019-07-17