3-125091463-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_024628.6(SLC12A8):c.1897C>T(p.Arg633Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000595 in 1,613,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000057 ( 0 hom. )
Consequence
SLC12A8
NM_024628.6 missense
NM_024628.6 missense
Scores
9
10
Clinical Significance
Conservation
PhyloP100: 2.19
Genes affected
SLC12A8 (HGNC:15595): (solute carrier family 12 member 8) This gene is thought to be a candidate for psoriasis susceptibility. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Sep 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21431825).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC12A8 | NM_024628.6 | c.1897C>T | p.Arg633Trp | missense_variant | 12/14 | ENST00000469902.6 | |
SLC12A8 | NM_001195483.2 | c.1897C>T | p.Arg633Trp | missense_variant | 11/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC12A8 | ENST00000469902.6 | c.1897C>T | p.Arg633Trp | missense_variant | 12/14 | 2 | NM_024628.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000855 AC: 13AN: 152066Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000321 AC: 8AN: 249324Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135278
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GnomAD4 exome AF: 0.0000568 AC: 83AN: 1461366Hom.: 0 Cov.: 30 AF XY: 0.0000564 AC XY: 41AN XY: 726998
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GnomAD4 genome AF: 0.0000854 AC: 13AN: 152184Hom.: 0 Cov.: 33 AF XY: 0.0000806 AC XY: 6AN XY: 74404
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 06, 2021 | The c.1897C>T (p.R633W) alteration is located in exon 12 (coding exon 11) of the SLC12A8 gene. This alteration results from a C to T substitution at nucleotide position 1897, causing the arginine (R) at amino acid position 633 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;.;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
.;M;M
MutationTaster
Benign
D;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;D;D
Vest4
MVP
MPC
0.045
ClinPred
T
GERP RS
Varity_R
gMVP
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