rs1459706

Positions:

• chr14-70044169-G-C

Variant summary

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

The NM_182932.3(SLC8A3):​c.*1778C>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0719 in 152,278 control chromosomes in the GnomAD database, including 423 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 0.072 (423 hom., cov: 32)
  • Exomes 𝑓: 0.083 (0 hom.)
• Consequence: SLC8A3 NM_182932.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.162

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.092 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC8A3	NM_182932.3	c.*1778C>G		downstream_gene_variant		ENST00000356921.7	NP_891977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC8A3	ENST00000356921.7	c.*1778C>G		downstream_gene_variant		1	NM_182932.3	ENSP00000349392.3
SLC8A3	ENST00000381269.6	c.*1778C>G		downstream_gene_variant		1		ENSP00000370669.2
SLC8A3	ENST00000494208.5	n.*2577C>G		downstream_gene_variant		1		ENSP00000436332.1

Frequencies

GnomAD3 genomes AF: 0.0720 AC: 10947 AN: 152136 Hom.: 423 Cov.: 32

Gnomad AFR AF: 0.0405

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0839

Gnomad ASJ AF: 0.0628

Gnomad EAS AF: 0.0133

Gnomad SAS AF: 0.0497

Gnomad FIN AF: 0.0805

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0939

Gnomad OTH AF: 0.0801

GnomAD4 exome AF: 0.0833 AC: 2 AN: 24 Hom.: 0 Cov.: 0 AF XY: 0.0556 AC XY: 1 AN XY: 18

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.111

GnomAD4 genome AF: 0.0719 AC: 10949 AN: 152254 Hom.: 423 Cov.: 32 AF XY: 0.0708 AC XY: 5273 AN XY: 74442

Gnomad4 AFR AF: 0.0404

Gnomad4 AMR AF: 0.0841

Gnomad4 ASJ AF: 0.0628

Gnomad4 EAS AF: 0.0131

Gnomad4 SAS AF: 0.0497

Gnomad4 FIN AF: 0.0805

Gnomad4 NFE AF: 0.0939

Gnomad4 OTH AF: 0.0792

Alfa AF: 0.0801 Hom.: 52

Bravo AF: 0.0718

Asia WGS AF: 0.0370 AC: 128 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.62

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1459706; hg19: chr14-70510886;