chr3-125092115-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024628.6(SLC12A8):​c.1789G>A​(p.Val597Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000054 in 1,611,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)
Exomes 𝑓: 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: 1.73
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.048802555).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC12A8NM_024628.6 linkuse as main transcriptc.1789G>A p.Val597Ile missense_variant 11/14 ENST00000469902.6
SLC12A8NM_001195483.2 linkuse as main transcriptc.1789G>A p.Val597Ile missense_variant 10/13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC12A8ENST00000469902.6 linkuse as main transcriptc.1789G>A p.Val597Ile missense_variant 11/142 NM_024628.6 P1A0AV02-1

Frequencies

GnomAD3 genomes
AF:
0.000237
AC:
36
AN:
152184
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000772
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000883
AC:
22
AN:
249228
Hom.:
0
AF XY:
0.0000518
AC XY:
7
AN XY:
135202
show subpopulations
Gnomad AFR exome
AF:
0.00123
Gnomad AMR exome
AF:
0.0000871
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000343
AC:
50
AN:
1459624
Hom.:
0
Cov.:
29
AF XY:
0.0000317
AC XY:
23
AN XY:
726210
show subpopulations
Gnomad4 AFR exome
AF:
0.00105
Gnomad4 AMR exome
AF:
0.0000672
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:
0.00000360
Gnomad4 OTH exome
AF:
0.000133
GnomAD4 genome
AF:
0.000243
AC:
37
AN:
152302
Hom.:
0
Cov.:
32
AF XY:
0.000215
AC XY:
16
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.000794
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000264
Hom.:
0
Bravo
AF:
0.000321
ESP6500AA
AF:
0.000268
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000579
AC:
7
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

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 GeneticsSep 16, 2021The c.1789G>A (p.V597I) alteration is located in exon 11 (coding exon 10) of the SLC12A8 gene. This alteration results from a G to A substitution at nucleotide position 1789, causing the valine (V) at amino acid position 597 to be replaced by an isoleucine (I). 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
0.076
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.19
CADD
Benign
16
DANN
Uncertain
1.0
DEOGEN2
Benign
0.053
.;T;T
Eigen
Benign
0.15
Eigen_PC
Uncertain
0.28
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.79
T;.;T
M_CAP
Benign
0.080
D
MetaRNN
Benign
0.049
T;T;T
MetaSVM
Uncertain
0.25
D
MutationAssessor
Uncertain
2.2
.;M;M
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-0.41
N;N;N
REVEL
Benign
0.26
Sift
Benign
0.23
T;T;T
Sift4G
Benign
0.074
T;T;T
Polyphen
0.75
P;B;B
Vest4
0.28
MVP
0.37
MPC
0.043
ClinPred
0.043
T
GERP RS
5.4
Varity_R
0.086
gMVP
0.34

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: rs373528909; hg19: chr3-124810959; API