chr3-125083991-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024628.6(SLC12A8):ā€‹c.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

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.60
Variant links:
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]

Genome browser will be placed here

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
SLC12A8NM_024628.6 linkuse as main transcriptc.2044G>C p.Glu682Gln missense_variant 14/14 ENST00000469902.6
SLC12A8NM_001195483.2 linkuse as main transcriptc.2044G>C p.Glu682Gln missense_variant 13/13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC12A8ENST00000469902.6 linkuse as main transcriptc.2044G>C p.Glu682Gln missense_variant 14/142 NM_024628.6 P1A0AV02-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152054
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000121
AC:
3
AN:
247892
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
134466
show subpopulations
Gnomad AFR exome
AF:
0.0000654
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000178
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000342
AC:
50
AN:
1461362
Hom.:
0
Cov.:
31
AF XY:
0.0000303
AC XY:
22
AN XY:
726904
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000387
Gnomad4 OTH exome
AF:
0.0000994
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152054
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74270
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000301
Hom.:
0
Bravo
AF:
0.0000227
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000118
AC:
1
ExAC
AF:
0.00000826
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 submitterclinical testingAmbry GeneticsApr 19, 2023The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.069
.;T;T
Eigen
Benign
0.14
Eigen_PC
Uncertain
0.22
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.83
T;.;T
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.15
T;T;T
MetaSVM
Uncertain
-0.12
T
MutationAssessor
Uncertain
2.3
.;M;M
MutationTaster
Benign
0.73
D;D;D;D;N
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-0.77
N;N;N
REVEL
Benign
0.24
Sift
Benign
0.41
T;T;T
Sift4G
Benign
0.067
T;T;T
Polyphen
0.98
D;B;B
Vest4
0.25
MVP
0.34
MPC
0.096
ClinPred
0.15
T
GERP RS
4.5
Varity_R
0.077
gMVP
0.53

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs373256263; hg19: chr3-124802835; COSMIC: COSV58871296; COSMIC: COSV58871296; API