rs4899329

chr14-70153925-C-Achr14-70153925-C-Gchr14-70153925-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182932.3(SLC8A3):c.1784+12714G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 152,192 control chromosomes in the GnomAD database, including 33,477 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.65 (33477 hom., cov: 33)
• Consequence: SLC8A3 NM_182932.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.141

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC8A3	NM_182932.3	c.1784+12714G>T		intron_variant		ENST00000356921.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC8A3	ENST00000356921.7	c.1784+12714G>T		intron_variant		1	NM_182932.3	A1

Frequencies

GnomAD3 genomes AF: 0.652 AC: 99177 AN: 152074 Hom.: 33462 Cov.: 33

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.958

Gnomad SAS AF: 0.841

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.637

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.652 AC: 99239 AN: 152192 Hom.: 33477 Cov.: 33 AF XY: 0.654 AC XY: 48687 AN XY: 74396

Gnomad4 AFR AF: 0.784

Gnomad4 AMR AF: 0.568

Gnomad4 ASJ AF: 0.657

Gnomad4 EAS AF: 0.958

Gnomad4 SAS AF: 0.840

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.573

Gnomad4 OTH AF: 0.640

Alfa AF: 0.595 Hom.: 35185

Bravo AF: 0.657

Asia WGS AF: 0.876 AC: 3048 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	6.1
Dann	Benign	0.89

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

Other links and lift over

dbSNP: rs4899329; hg19: chr14-70620642;