14-70050466-T-G

Position:

• chr14-70050466-T-G

Variant summary

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

The NM_182932.3(SLC8A3):​c.2113+542A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 151,912 control chromosomes in the GnomAD database, including 14,413 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 0.43 (14413 hom., cov: 32)
• Consequence: SLC8A3 NM_182932.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC8A3	NM_182932.3	c.2113+542A>C		intron_variant		ENST00000356921.7	NP_891977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC8A3	ENST00000356921.7	c.2113+542A>C		intron_variant		1	NM_182932.3	ENSP00000349392.3

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65117 AN: 151794 Hom.: 14393 Cov.: 32

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.427

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

GnomAD4 genome AF: 0.429 AC: 65177 AN: 151912 Hom.: 14413 Cov.: 32 AF XY: 0.425 AC XY: 31591 AN XY: 74256

Gnomad4 AFR AF: 0.557

Gnomad4 AMR AF: 0.355

Gnomad4 ASJ AF: 0.455

Gnomad4 EAS AF: 0.458

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.384

Gnomad4 OTH AF: 0.423

Alfa AF: 0.379 Hom.: 16229

Bravo AF: 0.435

Asia WGS AF: 0.367 AC: 1277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.8
DANN	Benign	0.66

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: rs12883884; hg19: chr14-70517183;