rs786204730
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000441.2(SLC26A4):c.365del(p.Phe122SerfsTer4) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,770 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. A120A) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000441.2 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC26A4 | NM_000441.2 | c.365del | p.Phe122SerfsTer4 | frameshift_variant | 4/21 | ENST00000644269.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC26A4 | ENST00000644269.2 | c.365del | p.Phe122SerfsTer4 | frameshift_variant | 4/21 | NM_000441.2 | P1 | ||
SLC26A4 | ENST00000440056.1 | c.365del | p.Phe122SerfsTer4 | frameshift_variant | 4/4 | 4 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460770Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1AN XY: 726758
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | May 14, 2020 | Loss-of-function variants in SLC26A4 are known to be pathogenic (PMID: 16283880, 25394566, 26252218, 26445815). For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with nonsyndromic enlargement of vestibular aqueduct (PMID: 25372295). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Phe122Serfs*4) in the SLC26A4 gene. It is expected to result in an absent or disrupted protein product. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.