rs151200437
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_198999.3(SLC26A5):āc.498T>Cā(p.Asn166=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000337 in 1,614,056 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00026 ( 0 hom., cov: 32)
Exomes š: 0.00034 ( 3 hom. )
Consequence
SLC26A5
NM_198999.3 synonymous
NM_198999.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.71
Genes affected
SLC26A5 (HGNC:9359): (solute carrier family 26 member 5) This gene encodes a member of the SLC26A/SulP transporter family. The protein functions as a molecular motor in motile outer hair cells (OHCs) of the cochlea, inducing changes in cell length that act to amplify sound levels. The transmembrane protein is an incomplete anion transporter, and does not allow anions to cross the cell membrane but instead undergoes a conformational change in response to changes in intracellular Cl- levels that results in a change in cell length. The protein functions at microsecond rates, which is several orders of magnitude faster than conventional molecular motor proteins. Mutations in this gene are potential candidates for causing neurosensory deafness. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Nov 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
Variant 7-103411492-A-G is Benign according to our data. Variant chr7-103411492-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 48340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-103411492-A-G is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-1.71 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000263 (40/152172) while in subpopulation NFE AF= 0.000544 (37/68028). AF 95% confidence interval is 0.000405. There are 0 homozygotes in gnomad4. There are 17 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC26A5 | NM_198999.3 | c.498T>C | p.Asn166= | synonymous_variant | 6/20 | ENST00000306312.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC26A5 | ENST00000306312.8 | c.498T>C | p.Asn166= | synonymous_variant | 6/20 | 1 | NM_198999.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000263 AC: 40AN: 152172Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000422 AC: 106AN: 251372Hom.: 0 AF XY: 0.000397 AC XY: 54AN XY: 135854
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GnomAD4 exome AF: 0.000345 AC: 504AN: 1461884Hom.: 3 Cov.: 31 AF XY: 0.000342 AC XY: 249AN XY: 727244
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GnomAD4 genome ? AF: 0.000263 AC: 40AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.000229 AC XY: 17AN XY: 74328
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 17, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 12, 2023 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 30, 2012 | Asn166Asn in Exon 06 of SLC26A5: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 3/7020 European Ame rican chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs151200437). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at