rs111033193
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BS1_SupportingBP4BP7
This summary comes from the ClinGen Evidence Repository: The SLC26A4 p.Asn538Asn variant has been reported in the heterozygous state in one individual with unilateral hearing loss (PMID:20621367). However, this variant is synonymous and is not predicted by computational prediction analysis, using MaxEntScan, to impact splicing (BP4, BP7). The filtering allele frequency (the lower threshold of the 95% CI of 60/24964) of the p.Asn538Asn variant in SLC26A4 is 0.19168% for African chromosomes in gnomAD, 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; http://gnomad.broadinstitute.org). This variant has also been reported in ClinVar (Variation ID 43517). 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, BP7. LINK:https://erepo.genome.network/evrepo/ui/classification/CA132671/MONDO:0010134/005
Frequency
Consequence
NM_000441.2 splice_region, synonymous
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC26A4 | ENST00000644269.2 | c.1614C>T | p.Asn538Asn | splice_region_variant, synonymous_variant | Exon 14 of 21 | NM_000441.2 | ENSP00000494017.1 | |||
SLC26A4 | ENST00000477350.5 | n.461C>T | splice_region_variant, non_coding_transcript_exon_variant | Exon 4 of 5 | 4 | |||||
SLC26A4 | ENST00000480841.5 | n.463C>T | splice_region_variant, non_coding_transcript_exon_variant | Exon 5 of 8 | 3 | |||||
SLC26A4 | ENST00000644846.1 | n.324C>T | splice_region_variant, non_coding_transcript_exon_variant | Exon 4 of 10 | ENSP00000494344.1 |
Frequencies
GnomAD3 genomes AF: 0.000631 AC: 96AN: 152088Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000215 AC: 54AN: 251058Hom.: 0 AF XY: 0.000147 AC XY: 20AN XY: 135686
GnomAD4 exome AF: 0.0000827 AC: 119AN: 1439706Hom.: 0 Cov.: 26 AF XY: 0.0000669 AC XY: 48AN XY: 717756
GnomAD4 genome AF: 0.000631 AC: 96AN: 152206Hom.: 0 Cov.: 32 AF XY: 0.000564 AC XY: 42AN XY: 74432
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:3
- -
- -
- -
This variant is associated with the following publications: (PMID: 30245029, 20621367) -
Pendred syndrome Uncertain:1Benign:2
- -
The SLC26A4 p.Asn538Asn variant has been reported in the heterozygous state in one individual with unilateral hearing loss (PMID: 20621367). However, this variant is synonymous and is not predicted by computational prediction analysis, using MaxEntScan, to impact splicing (BP4, BP7). The filtering allele frequency (the lower threshold of the 95% CI of 60/24964) of the p.Asn538Asn variant in SLC26A4 is 0.19168% for African chromosomes in gnomAD, 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; http://gnomad.broadinstitute.org). This variant has also been reported in ClinVar (Variation ID 43517). 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, BP7. -
- -
not specified Benign:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at