rs1035717

Variant names:

• chr14-70111982-A-G
• rs1035717
• NM_182932.3:c.1785-51043T>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.1785-51043T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 152,048 control chromosomes in the GnomAD database, including 16,443 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 0.45 (16443 hom., cov: 32)
• Consequence: SLC8A3 NM_182932.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.926 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.1785-51043T>C		intron	N/A	NP_891977.1
	SLC8A3	NM_183002.3		c.1785-51043T>C		intron	N/A	NP_892114.1
	SLC8A3	NM_033262.5		c.1785-48053T>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.1785-51043T>C		intron	N/A	ENSP00000349392.3
	SLC8A3	ENST00000381269.6	TSL:1	c.1785-51043T>C		intron	N/A	ENSP00000370669.2
	SLC8A3	ENST00000528359.6	TSL:1	c.1785-48053T>C		intron	N/A	ENSP00000433531.1

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68868 AN: 151930 Hom.: 16430 Cov.: 32

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.948

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.426

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

GnomAD4 genome AF: 0.453 AC: 68912 AN: 152048 Hom.: 16443 Cov.: 32 AF XY: 0.460 AC XY: 34223 AN XY: 74338

African (AFR) AF: 0.414 AC: 17175 AN: 41460

American (AMR) AF: 0.456 AC: 6969 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1794 AN: 3468

East Asian (EAS) AF: 0.948 AC: 4893 AN: 5160

South Asian (SAS) AF: 0.696 AC: 3354 AN: 4818

European-Finnish (FIN) AF: 0.437 AC: 4624 AN: 10586

Middle Eastern (MID) AF: 0.425 AC: 124 AN: 292

European-Non Finnish (NFE) AF: 0.423 AC: 28726 AN: 67966

Other (OTH) AF: 0.431 AC: 910 AN: 2112

Alfa AF: 0.437 Hom.: 25415

Bravo AF: 0.453

Asia WGS AF: 0.789 AC: 2741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.50
PhyloP100		-0.13
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: rs1035717; hg19: chr14-70578699;