rs1459706

Variant names:

• chr14-70044169-G-C
• rs1459706
• NM_182932.3:c.*1778C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182932.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC8A3	NM_182932.3	MANE Select	c.*1778C>G		downstream_gene	N/A	NP_891977.1	P57103-2
	SLC8A3	NM_183002.3		c.*1778C>G		downstream_gene	N/A	NP_892114.1	P57103-1
	SLC8A3	NM_033262.5		c.*1778C>G		downstream_gene	N/A	NP_150287.1	P57103-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC8A3	ENST00000356921.7	TSL:1 MANE Select	c.*1778C>G		downstream_gene	N/A	ENSP00000349392.3	P57103-2
	SLC8A3	ENST00000381269.6	TSL:1	c.*1778C>G		downstream_gene	N/A	ENSP00000370669.2	P57103-1
	SLC8A3	ENST00000216568.11	TSL:1	c.*1778C>G		downstream_gene	N/A	ENSP00000216568.7	P57103-5

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

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.111 AC: 2 AN: 18

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0404 AC: 1678 AN: 41552

American (AMR) AF: 0.0841 AC: 1286 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0628 AC: 218 AN: 3472

East Asian (EAS) AF: 0.0131 AC: 68 AN: 5190

South Asian (SAS) AF: 0.0497 AC: 240 AN: 4828

European-Finnish (FIN) AF: 0.0805 AC: 853 AN: 10590

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0939 AC: 6387 AN: 68008

Other (OTH) AF: 0.0792 AC: 167 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.62
PhyloP100		0.16

Splicing

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

Other links and lift over

dbSNP: rs1459706; hg19: chr14-70510886;