rs1163642957
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_000441.2(SLC26A4):āc.1570A>Cā(p.Ile524Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. I524I) has been classified as Likely benign.
Frequency
Consequence
NM_000441.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC26A4 | NM_000441.2 | c.1570A>C | p.Ile524Leu | missense_variant | 14/21 | ENST00000644269.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC26A4 | ENST00000644269.2 | c.1570A>C | p.Ile524Leu | missense_variant | 14/21 | NM_000441.2 | P1 | ||
SLC26A4 | ENST00000477350.5 | n.417A>C | non_coding_transcript_exon_variant | 4/5 | 4 | ||||
SLC26A4 | ENST00000480841.5 | n.419A>C | non_coding_transcript_exon_variant | 5/8 | 3 | ||||
SLC26A4 | ENST00000644846.1 | c.283A>C | p.Ile95Leu | missense_variant, NMD_transcript_variant | 4/10 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1458490Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1AN XY: 725874
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 16, 2016 | The p.Ile524Leu variant in SLC26A4 has not been previously reported in individua ls with hearing loss or in large population studies. Computational prediction to ols and conservation analyses suggest that this variant may not impact the prote in, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of the p.Ile524Leu variant is uncertain. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at