rs999618

Positions:

• chr14-70160549-T-C

Variant summary

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

The ENST00000356921.7(SLC8A3):​c.1784+6090A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,078 control chromosomes in the GnomAD database, including 2,483 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 0.17 (2483 hom., cov: 31)
• Consequence: SLC8A3 ENST00000356921.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC8A3	NM_182932.3	c.1784+6090A>G		intron_variant		ENST00000356921.7	NP_891977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC8A3	ENST00000356921.7	c.1784+6090A>G		intron_variant		1	NM_182932.3	ENSP00000349392	A1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25118 AN: 151958 Hom.: 2485 Cov.: 31

Gnomad AFR AF: 0.0872

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.0352

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.165 AC: 25113 AN: 152078 Hom.: 2483 Cov.: 31 AF XY: 0.161 AC XY: 11990 AN XY: 74318

Gnomad4 AFR AF: 0.0871

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.0349

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.224

Gnomad4 OTH AF: 0.187

Alfa AF: 0.203 Hom.: 1724

Bravo AF: 0.158

Asia WGS AF: 0.0780 AC: 271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.3
DANN	Benign	0.57

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: rs999618; hg19: chr14-70627266;