rs375716219
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 4P and 5B. PM1PM2BP4_StrongBP6
The NM_000441.2(SLC26A4):āc.61A>Gā(p.Met21Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000299 in 1,571,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000441.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC26A4 | NM_000441.2 | c.61A>G | p.Met21Val | missense_variant | 2/21 | ENST00000644269.2 | |
SLC26A4-AS1 | NR_028137.1 | n.97T>C | non_coding_transcript_exon_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC26A4 | ENST00000644269.2 | c.61A>G | p.Met21Val | missense_variant | 2/21 | NM_000441.2 | P1 | ||
SLC26A4-AS1 | ENST00000668981.1 | n.157T>C | non_coding_transcript_exon_variant | 1/2 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152182Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000330 AC: 6AN: 181734Hom.: 0 AF XY: 0.0000507 AC XY: 5AN XY: 98670
GnomAD4 exome AF: 0.0000254 AC: 36AN: 1418838Hom.: 0 Cov.: 30 AF XY: 0.0000342 AC XY: 24AN XY: 702600
GnomAD4 genome AF: 0.0000723 AC: 11AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74348
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 21 of the SLC26A4 protein (p.Met21Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with SLC26A4-related conditions. ClinVar contains an entry for this variant (Variation ID: 505477). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies have shown that this missense change does not substantially affect SLC26A4 function (PMID: 29320412). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 17, 2017 | p.Met21Val in exon 2 of SLC26A4: This variant is not expected to have clinical s ignificance due to a lack of conservation across species, including mammals. Of note, >40 mammals have a valine at this position despite high nearby amino acid conservation. In addition, computational prediction tools do not suggest a high likelihood of impact to the protein. It has also been identified in 0.15% (3/199 2) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac .broadinstitute.org; dbSNP rs375716219). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at