chr3-125083915-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.2120G>A​(p.Arg707Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,612,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

SLC12A8
NM_024628.6 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.738
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=0.043896466).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC12A8NM_024628.6 linkuse as main transcriptc.2120G>A p.Arg707Gln missense_variant 14/14 ENST00000469902.6
SLC12A8NM_001195483.2 linkuse as main transcriptc.2120G>A p.Arg707Gln missense_variant 13/13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC12A8ENST00000469902.6 linkuse as main transcriptc.2120G>A p.Arg707Gln missense_variant 14/142 NM_024628.6 P1A0AV02-1

Frequencies

GnomAD3 genomes
AF:
0.0000592
AC:
9
AN:
151924
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000484
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000445
AC:
11
AN:
247182
Hom.:
0
AF XY:
0.0000298
AC XY:
4
AN XY:
134050
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000582
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000392
Gnomad SAS exome
AF:
0.0000331
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000892
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000205
AC:
30
AN:
1460986
Hom.:
0
Cov.:
31
AF XY:
0.0000165
AC XY:
12
AN XY:
726648
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.0000465
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000144
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000592
AC:
9
AN:
151924
Hom.:
0
Cov.:
31
AF XY:
0.0000809
AC XY:
6
AN XY:
74164
show subpopulations
Gnomad4 AFR
AF:
0.0000484
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000478
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.0000743
AC:
9
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

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 GeneticsDec 17, 2023The c.2120G>A (p.R707Q) 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 2120, causing the arginine (R) at amino acid position 707 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
0.076
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
12
DANN
Uncertain
0.98
DEOGEN2
Benign
0.070
.;T;T
Eigen
Benign
-0.67
Eigen_PC
Benign
-0.67
FATHMM_MKL
Benign
0.57
D
LIST_S2
Benign
0.72
T;.;T
M_CAP
Benign
0.075
D
MetaRNN
Benign
0.044
T;T;T
MetaSVM
Benign
-0.57
T
MutationAssessor
Benign
1.7
.;L;L
MutationTaster
Benign
1.0
N;N;N;N;N
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-0.81
N;N;N
REVEL
Benign
0.24
Sift
Benign
0.15
T;T;T
Sift4G
Benign
0.24
T;T;T
Polyphen
0.96
D;P;P
Vest4
0.12
MutPred
0.27
.;Gain of helix (P = 0.1736);Gain of helix (P = 0.1736);
MVP
0.20
MPC
0.050
ClinPred
0.037
T
GERP RS
1.2
Varity_R
0.029
gMVP
0.50

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: rs771546073; hg19: chr3-124802759; API