14-70051107-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_182932.3(SLC8A3):​c.2014A>G​(p.Thr672Ala) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SLC8A3
NM_182932.3 missense, splice_region

Scores

2
17
Splicing: ADA: 0.0001194
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.05
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1
In a binding_site (size 0) in uniprot entity NAC3_HUMAN
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.12953103).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC8A3NM_182932.3 linkuse as main transcriptc.2014A>G p.Thr672Ala missense_variant, splice_region_variant 5/7 ENST00000356921.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC8A3ENST00000356921.7 linkuse as main transcriptc.2014A>G p.Thr672Ala missense_variant, splice_region_variant 5/71 NM_182932.3 A1P57103-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
28
GnomAD4 genome
Cov.:
32

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 GeneticsNov 21, 2022The c.2032A>G (p.T678A) alteration is located in exon 6 (coding exon 5) of the SLC8A3 gene. This alteration results from a A to G substitution at nucleotide position 2032, causing the threonine (T) at amino acid position 678 to be replaced by an alanine (A). 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
0.078
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
22
DANN
Uncertain
0.97
DEOGEN2
Benign
0.13
.;T;.;.;.;.;.;.
Eigen
Benign
-0.44
Eigen_PC
Benign
-0.23
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Benign
0.85
T;T;D;T;T;T;.;T
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.13
T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
-0.90
.;N;.;.;.;.;.;.
MutationTaster
Benign
0.70
D;D;D;N;N;N;N;N
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-1.2
N;N;N;N;N;N;N;N
REVEL
Benign
0.066
Sift
Benign
0.19
T;T;T;T;T;T;T;T
Sift4G
Benign
0.34
T;T;T;T;T;T;T;D
Polyphen
0.0
B;B;.;.;.;.;.;B
Vest4
0.36
MutPred
0.37
.;Loss of sheet (P = 0.0142);.;.;.;.;.;.;
MVP
0.25
MPC
0.16
ClinPred
0.54
D
GERP RS
3.1
Varity_R
0.072
gMVP
0.12

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00012
dbscSNV1_RF
Benign
0.0040
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-70517824; API