chr3-125083942-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024628.6(SLC12A8):​c.2093G>A​(p.Arg698His) variant causes a missense change. The variant allele was found at a frequency of 0.0000347 in 1,613,406 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R698P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

SLC12A8
NM_024628.6 missense

Scores

2
10
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.61
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC12A8NM_024628.6 linkuse as main transcriptc.2093G>A p.Arg698His missense_variant 14/14 ENST00000469902.6
SLC12A8NM_001195483.2 linkuse as main transcriptc.2093G>A p.Arg698His missense_variant 13/13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC12A8ENST00000469902.6 linkuse as main transcriptc.2093G>A p.Arg698His missense_variant 14/142 NM_024628.6 P1A0AV02-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
151950
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:
0.0000202
AC:
5
AN:
248064
Hom.:
0
AF XY:
0.0000149
AC XY:
2
AN XY:
134546
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.0000444
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000356
AC:
52
AN:
1461456
Hom.:
0
Cov.:
31
AF XY:
0.0000261
AC XY:
19
AN XY:
726970
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:
0.0000187
Gnomad4 NFE exome
AF:
0.0000441
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
151950
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74186
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:
0.0000564
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.0000165
AC:
2

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 GeneticsMar 25, 2024The c.2093G>A (p.R698H) alteration is located in exon 14 (coding exon 13) of the SLC12A8 gene. This alteration results from a G to A substitution at nucleotide position 2093, causing the arginine (R) at amino acid position 698 to be replaced by a histidine (H). 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
0.19
BayesDel_addAF
Benign
-0.013
T
BayesDel_noAF
Benign
-0.13
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.32
.;T;T
Eigen
Uncertain
0.33
Eigen_PC
Uncertain
0.26
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.78
T;.;T
M_CAP
Uncertain
0.15
D
MetaRNN
Uncertain
0.48
T;T;T
MetaSVM
Uncertain
0.18
D
MutationAssessor
Pathogenic
2.9
.;M;M
MutationTaster
Benign
0.76
D;D;D;D;N
PrimateAI
Benign
0.38
T
PROVEAN
Uncertain
-3.3
D;D;D
REVEL
Uncertain
0.51
Sift
Uncertain
0.019
D;D;D
Sift4G
Uncertain
0.020
D;D;D
Polyphen
1.0
D;D;D
Vest4
0.31
MutPred
0.56
.;Gain of glycosylation at T695 (P = 0.0306);Gain of glycosylation at T695 (P = 0.0306);
MVP
0.79
MPC
0.33
ClinPred
0.92
D
GERP RS
3.3
Varity_R
0.039
gMVP
0.72

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: rs776564193; hg19: chr3-124802786; API