The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

  • See Evidence submitted by expert panel for details.

Variant: NM_000441.2(SLC26A4):c.147C>G (p.Ser49Arg)

CA4432373

227949 (ClinVar)

Gene: SLC26A4
Condition: Pendred syndrome
Inheritance Mode: Autosomal recessive inheritance
UUID: 714cab10-9700-444a-be53-9f2758251da9

HGVS expressions

NM_000441.2:c.147C>G
NM_000441.2(SLC26A4):c.147C>G (p.Ser49Arg)
NM_000441.1:c.147C>G
NR_028137.1:n.11G>C
ENST00000265715.7:c.147C>G
ENST00000440056.1:c.147C>G
NC_000007.14:g.107661788C>G
CM000669.2:g.107661788C>G
NC_000007.13:g.107302233C>G
CM000669.1:g.107302233C>G
NC_000007.12:g.107089469C>G
NG_008489.1:g.6154C>G

Likely Benign

Met criteria codes 2
BP4 BS1_Supporting
Not Met criteria codes 11
PS1 PS3 PS4 PP3 PP1 PM5 PM1 PM3 PM2 BS2 BS4

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Hearing Loss VCEP
The SLC26A4 p.Ser49Arg variant has been identified in a heterozygous state in two Chinese individuals with congenital non-syndromic hearing loss (PMID: 25149764). No information about segregation of the variant or whether it was in trans with another SLC26A4 variant was given. The filtering allele frequency of the p.Ser49Arg variant in the SLC26A4 gene is 0.27% for East Asian chromosomes by gnomAD (44/12282 with 95% CI), which is a higher frequency than would be expected for an autosomal recessive pathogenic variant based on the thresholds defined by the ClinGen Hearing Loss Expert Panel (BS1_Supporting). Additionally, computational prediction analysis using the metapredictor tool REVEL suggests that the variant may not impact the protein (BP4). Splice prediction analysis using MaxEntScan does not suggest an impact to splicing (BP4). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel : BS1_Supporting, BP4.
Met criteria codes
BP4
REVEL score 0.108, no splicing imact predicted, nucleotide not conserved, but animo acid moderately conserved.
BS1_Supporting
the filtering allele frequency of the p.Ser49Arg variant in the SLC26A4 gene is 0.27% for East Asian chromosomes by gnomAD (44/12282 with 95% CI),
Not Met criteria codes
PS1
The current variant is the only variant found in this codon in ClinVar.
PS3
No functional studies were performed for this variant.
PS4
Case-control analysis was not performed. This variant has a higher MAF in the East Asian population (gnomAD).
PP3
REVEL score 0.108
PP1
No segregation was performed.
PM5
The current variant is the only variant found in this codon in ClinVar.
PM1
Does not impact a protein domain.
PM3
The variant has been identified in a heterozygous state in two Chinese individuals with congenital non-syndromic hearing loss (PMID: 25149764). No information about segregation of the variant or whether it was in trans with another SLC26A4 variant was given.
PM2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
No homozygous individuals in gnomAD with this variant have been reported.
BS4
No segregation was performed.
Approved on: 2019-10-02
Published on: 2019-10-31
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.