Variant: NM_000441.1(SLC26A4):c.2291C>T (p.Thr764Met)

CA132713

43546 (ClinVar)

Gene: SLC26A4

Condition: Pendred syndrome

Inheritance Mode: Autosomal recessive inheritance

UUID: edaf7951-7b12-42e2-855d-4a2dc61b69c8

HGVS expressions

NM_000441.1:c.2291C>T
NM_000441.1(SLC26A4):c.2291C>T (p.Thr764Met)
NC_000007.14:g.107712594C>T
CM000669.2:g.107712594C>T
NC_000007.13:g.107353039C>T
CM000669.1:g.107353039C>T
NC_000007.12:g.107140275C>T
NG_008489.1:g.56960C>T
ENST00000265715.7:c.2291C>T
ENST00000492030.2:n.477C>T

Uncertain Significance

• Met criteria codes: PM2_Supporting

• Not Met criteria codes: PS1 PS3 PS4 PS2 PP3 PP1 PP4 PVS1 PM6 PM5 PM4 PM1 PM3 BA1 BS2 BS1 BS4 BP7 BP5 BP4 BP3 BP2

Expert Panel

Hearing Loss VCEP

Criteria Specification Information

Evidence submitted by expert panel

Hearing Loss VCEP

The allele frequency of the p.Thr764Met variant in SLC26A4 is 0.01% (3/24024) of African alleles and 0.007% (9/126592) of European (Non-Finnish) alleles by the Genome Aggregation Database (http://gnomad.broadinstitute.org), which is a low enough frequency to award PM2_Supporting based on the thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss (PM2_P). However, rarity/absence alone does not support a pathogenic classification. In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: PM2_P.

Met criteria codes

• PM2_Supporting: The variant is present in 0.01% of African alleles and 0.007% of European (Non-Finnish) alleles in gnomAD

Not Met criteria codes

• PS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PVS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM6: 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
• PM4: 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
• PM3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BA1: The variant is present in 0.01% of African alleles and 0.007% of European (Non-Finnish) alleles in gnomAD
• BS2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS1: The variant is present in 0.01% of African alleles and 0.007% of European (Non-Finnish) alleles in gnomAD
• BS4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP7: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP5: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP2: 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