Variant chr14-70048859-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_182932.3(SLC8A3):c.2297T>C(p.Ile766Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000571 in 1,614,168 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00050 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00058 ( 1 hom. )

Consequence

SLC8A3
NM_182932.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.25

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4013394).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC8A3	NM_182932.3 linkuse as main transcript	c.2297T>C	p.Ile766Thr	missense_variant	6/7	ENST00000356921.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC8A3	ENST00000356921.7 linkuse as main transcript	c.2297T>C	p.Ile766Thr	missense_variant	6/7	1	NM_182932.3	A1	P57103-2

Frequencies

GnomAD3 genomes

AF:

0.000499

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

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:

0.000750

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000390

AC:

AN:

251230

Hom.:

AF XY:

0.000412

AC XY:

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.000492

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000572

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000579

AC:

846

AN:

1461812

Hom.:

Cov.:

AF XY:

0.000586

AC XY:

426

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.000559

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000688

Gnomad4 OTH exome

AF:

0.000480

GnomAD4 genome

AF:

0.000499

AC:

AN:

152356

Hom.:

Cov.:

AF XY:

0.000483

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.000264

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000750

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000682

Hom.:

Bravo

AF:

0.000525

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000436

AC:

EpiCase

AF:

0.000927

EpiControl

AF:

0.000771

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

Aug 30, 2021

The c.2315T>C (p.I772T) alteration is located in exon 7 (coding exon 6) of the SLC8A3 gene. This alteration results from a T to C substitution at nucleotide position 2315, causing the isoleucine (I) at amino acid position 772 to be replaced by a threonine (T). 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

0.30

BayesDel_addAF

Uncertain

0.016

BayesDel_noAF

Pathogenic

0.21

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.59

.;D;.;.;.;.;.;.

Eigen

Uncertain

0.66

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.96

D;D;D;D;D;D;.;D

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.40

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

MetaSVM

Uncertain

-0.13

MutationAssessor

Benign

1.8

.;L;.;.;.;.;.;.

MutationTaster

Benign

1.0

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

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-2.6

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

REVEL

Uncertain

0.59

Sift

Benign

0.091

T;T;T;T;T;T;T;D

Sift4G

Benign

0.10

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

Polyphen

0.99

D;D;.;.;.;.;.;B

Vest4

0.95

MVP

0.65

MPC

0.45

ClinPred

0.046

GERP RS

5.8

Varity_R

0.30

gMVP

0.80

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