3-125107580-T-C

Variant summary

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

The NM_024628.6(SLC12A8):ā€‹c.1606A>Gā€‹(p.Asn536Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)

Consequence

SLC12A8
NM_024628.6 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.297
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=0.0460577).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC12A8NM_024628.6 linkuse as main transcriptc.1606A>G p.Asn536Asp missense_variant 10/14 ENST00000469902.6
SLC12A8NM_001195483.2 linkuse as main transcriptc.1606A>G p.Asn536Asp missense_variant 9/13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC12A8ENST00000469902.6 linkuse as main transcriptc.1606A>G p.Asn536Asp missense_variant 10/142 NM_024628.6 P1A0AV02-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152178
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000401
AC:
1
AN:
249572
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135400
show subpopulations
Gnomad AFR exome
AF:
0.0000646
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
32
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152178
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.00000826
AC:
1

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 GeneticsFeb 22, 2023The c.1606A>G (p.N536D) alteration is located in exon 10 (coding exon 9) of the SLC12A8 gene. This alteration results from a A to G substitution at nucleotide position 1606, causing the asparagine (N) at amino acid position 536 to be replaced by an aspartic acid (D). 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
-0.46
CADD
Benign
6.8
DANN
Benign
0.97
DEOGEN2
Benign
0.031
.;T;T
Eigen
Benign
-0.85
Eigen_PC
Benign
-0.81
FATHMM_MKL
Benign
0.055
N
LIST_S2
Benign
0.45
T;.;T
M_CAP
Benign
0.043
D
MetaRNN
Benign
0.046
T;T;T
MetaSVM
Benign
-0.77
T
MutationAssessor
Benign
1.6
.;L;L
MutationTaster
Benign
1.0
N;N;N;N;N
PrimateAI
Benign
0.32
T
PROVEAN
Benign
0.10
N;N;N
REVEL
Benign
0.063
Sift
Benign
0.31
T;T;T
Sift4G
Benign
0.49
T;T;T
Polyphen
0.0030
B;B;B
Vest4
0.071
MutPred
0.15
.;Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);
MVP
0.28
MPC
0.047
ClinPred
0.046
T
GERP RS
1.8
Varity_R
0.074
gMVP
0.091

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: rs778092307; hg19: chr3-124826424; API