rs431905517
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5
The NM_198999.3(SLC26A5):āc.390A>Cā(p.Arg130Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,312 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 Pathogenic (no stars).
Frequency
Genomes: not found (cov: 31)
Exomes š: 6.9e-7 ( 0 hom. )
Consequence
SLC26A5
NM_198999.3 missense
NM_198999.3 missense
Scores
8
7
3
Clinical Significance
Conservation
PhyloP100: 0.188
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 Uncertain_significance. Variant got 5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.883
PP5
?
Variant 7-103413015-T-G is Pathogenic according to our data. Variant chr7-103413015-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 97020.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr7-103413015-T-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC26A5 | NM_198999.3 | c.390A>C | p.Arg130Ser | missense_variant | 5/20 | ENST00000306312.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC26A5 | ENST00000306312.8 | c.390A>C | p.Arg130Ser | missense_variant | 5/20 | 1 | NM_198999.3 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome AF: 6.88e-7 AC: 1AN: 1454312Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 723972
GnomAD4 exome
AF:
AC:
1
AN:
1454312
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
723972
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Autosomal recessive nonsyndromic hearing loss 61 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 28, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;.;D;D;D;.;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;M;M;M;M;M;.;.;M
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D;D;D;.;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D;D;D;D;.;D;D
Sift4G
Uncertain
D;D;D;D;D;D;D;D;D
Polyphen
P;D;D;.;B;.;.;.;.
Vest4
MutPred
Gain of glycosylation at S133 (P = 0.1573);Gain of glycosylation at S133 (P = 0.1573);Gain of glycosylation at S133 (P = 0.1573);Gain of glycosylation at S133 (P = 0.1573);Gain of glycosylation at S133 (P = 0.1573);Gain of glycosylation at S133 (P = 0.1573);Gain of glycosylation at S133 (P = 0.1573);Gain of glycosylation at S133 (P = 0.1573);Gain of glycosylation at S133 (P = 0.1573);
MVP
MPC
0.23
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at