chr14-70061216-A-G

Variant names:

• chr14-70061216-A-G
• rs10136340
• NM_182932.3:c.1785-277T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182932.3(SLC8A3):​c.1785-277T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0904 in 152,226 control chromosomes in the GnomAD database, including 718 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 0.090 (718 hom., cov: 32)
• Consequence: SLC8A3 NM_182932.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.135 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC8A3	NM_182932.3	MANE Select	c.1785-277T>C		intron	N/A	NP_891977.1
	SLC8A3	NM_183002.3		c.1785-277T>C		intron	N/A	NP_892114.1
	SLC8A3	NM_033262.5		c.1891+2607T>C		intron	N/A	NP_150287.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC8A3	ENST00000356921.7	TSL:1 MANE Select	c.1785-277T>C		intron	N/A	ENSP00000349392.3
	SLC8A3	ENST00000381269.6	TSL:1	c.1785-277T>C		intron	N/A	ENSP00000370669.2
	SLC8A3	ENST00000528359.6	TSL:1	c.1891+2607T>C		intron	N/A	ENSP00000433531.1

Frequencies

GnomAD3 genomes AF: 0.0904 AC: 13747 AN: 152108 Hom.: 719 Cov.: 32

Gnomad AFR AF: 0.0485

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.0615

Gnomad ASJ AF: 0.0894

Gnomad EAS AF: 0.00500

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0777

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

GnomAD4 genome AF: 0.0904 AC: 13754 AN: 152226 Hom.: 718 Cov.: 32 AF XY: 0.0927 AC XY: 6898 AN XY: 74414

African (AFR) AF: 0.0485 AC: 2016 AN: 41560

American (AMR) AF: 0.0614 AC: 940 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0894 AC: 310 AN: 3466

East Asian (EAS) AF: 0.00482 AC: 25 AN: 5188

South Asian (SAS) AF: 0.144 AC: 692 AN: 4812

European-Finnish (FIN) AF: 0.168 AC: 1776 AN: 10590

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

European-Non Finnish (NFE) AF: 0.113 AC: 7673 AN: 67998

Other (OTH) AF: 0.0783 AC: 165 AN: 2108

Alfa AF: 0.0987 Hom.: 1599

Bravo AF: 0.0789

Asia WGS AF: 0.0820 AC: 283 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.57
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10136340; hg19: chr14-70527933;