chr3-125083991-C-G
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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):āc.2044G>Cā(p.Glu682Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000335 in 1,613,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000026 ( 0 hom., cov: 31)
Exomes š: 0.000034 ( 0 hom. )
Consequence
SLC12A8
NM_024628.6 missense
NM_024628.6 missense
Scores
5
14
Clinical Significance
Conservation
PhyloP100: 4.60
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=0.15157443).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC12A8 | NM_024628.6 | c.2044G>C | p.Glu682Gln | missense_variant | 14/14 | ENST00000469902.6 | |
SLC12A8 | NM_001195483.2 | c.2044G>C | p.Glu682Gln | missense_variant | 13/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC12A8 | ENST00000469902.6 | c.2044G>C | p.Glu682Gln | missense_variant | 14/14 | 2 | NM_024628.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152054Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000121 AC: 3AN: 247892Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134466
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GnomAD4 exome AF: 0.0000342 AC: 50AN: 1461362Hom.: 0 Cov.: 31 AF XY: 0.0000303 AC XY: 22AN XY: 726904
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152054Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74270
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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 | Apr 19, 2023 | The c.2044G>C (p.E682Q) alteration is located in exon 14 (coding exon 13) of the SLC12A8 gene. This alteration results from a G to C substitution at nucleotide position 2044, causing the glutamic acid (E) at amino acid position 682 to be replaced by a glutamine (Q). 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
Benign
DANN
Uncertain
DEOGEN2
Benign
.;T;T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
.;M;M
MutationTaster
Benign
D;D;D;D;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
D;B;B
Vest4
MVP
MPC
0.096
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