rs8020841

Positions:

• chr14-70045442-T-C

Variant summary

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

The ENST00000356921.7(SLC8A3):​c.*505A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,198 control chromosomes in the GnomAD database, including 5,189 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 0.26 (5184 hom., cov: 32)
  • Exomes 𝑓: 0.19 (5 hom.)
• Consequence: SLC8A3 ENST00000356921.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.462

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC8A3	NM_182932.3	c.*505A>G		3_prime_UTR_variant	7/7	ENST00000356921.7	NP_891977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC8A3	ENST00000356921.7	c.*505A>G		3_prime_UTR_variant	7/7	1	NM_182932.3	ENSP00000349392	A1

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38751 AN: 151848 Hom.: 5173 Cov.: 32

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.0574

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.250

GnomAD4 exome AF: 0.185 AC: 43 AN: 232 Hom.: 5 Cov.: 0 AF XY: 0.113 AC XY: 12 AN XY: 106

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.167

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.300

Gnomad4 NFE exome AF: 0.182

Gnomad4 OTH exome AF: 0.182

GnomAD4 genome AF: 0.255 AC: 38799 AN: 151966 Hom.: 5184 Cov.: 32 AF XY: 0.252 AC XY: 18738 AN XY: 74256

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.0572

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.246

Gnomad4 OTH AF: 0.249

Alfa AF: 0.240 Hom.: 4285

Bravo AF: 0.253

Asia WGS AF: 0.129 AC: 448 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	0.43
DANN	Benign	0.56

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: rs8020841; hg19: chr14-70512159;