Variant 14-70046172-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_182932.3(SLC8A3):c.2541G>C(p.Glu847Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000947 in 1,614,226 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0052 ( 10 hom., cov: 33)

Exomes 𝑓: 0.00051 ( 7 hom. )

Consequence

SLC8A3
NM_182932.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.04

Variant links:

Genes affected

SLC8A3 (HGNC:11070): (solute carrier family 8 member A3) This gene encodes a member of the sodium/calcium exchanger integral membrane protein family. Na+/Ca2+ exchange proteins are involved in maintaining Ca2+ homeostasis in a wide variety of cell types. The protein is regulated by intracellular calcium ions and is found in both the plasma membrane and intracellular organellar membranes, where exchange of Na+ for Ca2+ occurs in an electrogenic manner. Alternative splicing has been observed for this gene and multiple variants have been described. [provided by RefSeq, Aug 2013]

SLC8A3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0053912997).

BP6

Variant 14-70046172-C-G is Benign according to our data. Variant chr14-70046172-C-G is described in ClinVar as [Benign]. Clinvar id is 785465.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00518 (789/152364) while in subpopulation AFR AF= 0.0183 (760/41590). AF 95% confidence interval is 0.0172. There are 10 homozygotes in gnomad4. There are 384 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC8A3	NM_182932.3 linkuse as main transcript	c.2541G>C	p.Glu847Asp	missense_variant	7/7	ENST00000356921.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC8A3	ENST00000356921.7 linkuse as main transcript	c.2541G>C	p.Glu847Asp	missense_variant	7/7	1	NM_182932.3	A1	P57103-2

Frequencies

GnomAD3 genomes

AF:

0.00518

AC:

789

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0183

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

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:

0.00383

GnomAD3 exomes

AF:

0.00138

AC:

346

AN:

250776

Hom.:

AF XY:

0.000966

AC XY:

131

AN XY:

135628

show subpopulations

Gnomad AFR exome

AF:

0.0193

Gnomad AMR exome

AF:

0.000752

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.000506

AC:

739

AN:

1461862

Hom.:

Cov.:

AF XY:

0.000418

AC XY:

304

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0187

Gnomad4 AMR exome

AF:

0.000716

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.00111

GnomAD4 genome

AF:

0.00518

AC:

789

AN:

152364

Hom.:

Cov.:

AF XY:

0.00515

AC XY:

384

AN XY:

74524

show subpopulations

Gnomad4 AFR

AF:

0.0183

Gnomad4 AMR

AF:

0.00111

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:

0.00379

Alfa

AF:

0.000925

Hom.:

Bravo

AF:

0.00601

ESP6500AA

AF:

0.0188

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00171

AC:

208

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

.;T;.;.;.;.;.

Eigen

Benign

-0.051

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.75

T;T;T;T;T;T;.

MetaRNN

Benign

0.0054

T;T;T;T;T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

-0.51

.;N;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.83

N;N;N;N;N;N;N

REVEL

Benign

0.089

Sift

Benign

0.33

T;T;T;T;T;T;T

Sift4G

Benign

0.58

T;T;T;T;T;T;T

Polyphen

0.27

B;P;.;.;.;.;.

Vest4

0.079

MutPred

0.41

.;Gain of catalytic residue at A858 (P = 0.001);.;.;.;.;.;

MVP

0.47

MPC

0.23

ClinPred

0.016

GERP RS

3.6

Varity_R

0.18

gMVP

0.53

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