rs752807925
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000441.2(SLC26A4):c.2086C>T(p.Gln696*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000352 in 1,137,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000441.2 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC26A4 | ENST00000644269.2 | c.2086C>T | p.Gln696* | stop_gained | Exon 18 of 21 | NM_000441.2 | ENSP00000494017.1 | |||
SLC26A4 | ENST00000492030.2 | n.373C>T | non_coding_transcript_exon_variant | Exon 3 of 6 | 5 | |||||
SLC26A4 | ENST00000644846.1 | n.744+2325C>T | intron_variant | Intron 7 of 9 | ENSP00000494344.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000134 AC: 3AN: 223536Hom.: 0 AF XY: 0.0000167 AC XY: 2AN XY: 120070
GnomAD4 exome AF: 0.00000352 AC: 4AN: 1137102Hom.: 0 Cov.: 16 AF XY: 0.00000346 AC XY: 2AN XY: 578728
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Pendred syndrome Pathogenic:3
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Autosomal recessive nonsyndromic hearing loss 4 Pathogenic:3
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not provided Pathogenic:2
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 21961810, 24913939, 26252218, 30842343, 30275481, 31541171, 24612839, 22289209, 23918157) -
This sequence change creates a premature translational stop signal (p.Gln696*) in the SLC26A4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC26A4 are known to be pathogenic (PMID: 16283880, 25394566, 26252218, 26445815). This variant is present in population databases (rs752807925, gnomAD 0.02%). This premature translational stop signal has been observed in individuals with SLC26A4-related conditions (PMID: 21961810, 22289209, 26252218). ClinVar contains an entry for this variant (Variation ID: 189164). For these reasons, this variant has been classified as Pathogenic. -
Pendred syndrome;C3538946:Autosomal recessive nonsyndromic hearing loss 4 Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at