Variant 3-125083942-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_024628.6(SLC12A8):c.2093G>C(p.Arg698Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,454 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SLC12A8
NM_024628.6 missense

Scores

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]

SLC12A8 links:

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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	Protein	UniProt
SLC12A8	NM_024628.6 linkuse as main transcript	c.2093G>C	p.Arg698Pro	missense_variant	14/14	ENST00000469902.6	NP_078904.4
SLC12A8	NM_001195483.2 linkuse as main transcript	c.2093G>C	p.Arg698Pro	missense_variant	13/13		NP_001182412.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC12A8	ENST00000469902.6 linkuse as main transcript	c.2093G>C	p.Arg698Pro	missense_variant	14/14	2	NM_024628.6	ENSP00000418783	P1	A0AV02-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000806

AC:

AN:

248064

Hom.:

AF XY:

0.0000149

AC XY:

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:

0.000112

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:

0.00000274

AC:

AN:

1461454

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726968

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000577

AC:

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 submitter

clinical testing

Ambry Genetics

May 10, 2023

The c.2093G>C (p.R698P) 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 2093, causing the arginine (R) at amino acid position 698 to be replaced by a proline (P). 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

Pathogenic

0.74

BayesDel_addAF

Benign

-0.037

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.43

.;T;T

Eigen

Benign

0.074

Eigen_PC

Benign

0.079

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.83

T;.;T

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.67

D;D;D

MetaSVM

Uncertain

-0.0079

MutationAssessor

Uncertain

2.4

.;M;M

MutationTaster

Benign

0.90

D;D;D;D;N

PrimateAI

Benign

0.40

PROVEAN

Pathogenic

-4.7

D;D;D

REVEL

Uncertain

0.55

Sift

Benign

0.038

D;D;D

Sift4G

Benign

0.20

T;T;T

Polyphen

0.96

D;P;P

Vest4

0.61

MutPred

0.54

.;Gain of glycosylation at T695 (P = 0.0306);Gain of glycosylation at T695 (P = 0.0306);

MVP

0.83

MPC

0.16

ClinPred

0.94

GERP RS

3.3

Varity_R

0.24

gMVP

0.86

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over