rs17293432

Positions:

• chr20-19585027-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_020689.4(SLC24A3):​c.480G>A​(p.Ser160=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.078 in 1,613,488 control chromosomes in the GnomAD database, including 5,575 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 0.067 (425 hom., cov: 32)
  • Exomes 𝑓: 0.079 (5150 hom.)
• Consequence: SLC24A3 NM_020689.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.58

Genes affected

SLC24A3 (HGNC:10977): (solute carrier family 24 member 3) Plasma membrane sodium/calcium exchangers are an important component of intracellular calcium homeostasis and electrical conduction. Potassium-dependent sodium/calcium exchangers such as SLC24A3 are believed to transport 1 intracellular calcium and 1 potassium ion in exchange for 4 extracellular sodium ions (Kraev et al., 2001 [PubMed 11294880]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=-3.58 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.087 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC24A3	NM_020689.4	c.480G>A	p.Ser160=	synonymous_variant	5/17	ENST00000328041.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC24A3	ENST00000328041.11	c.480G>A	p.Ser160=	synonymous_variant	5/17	1	NM_020689.4	P1

Frequencies

GnomAD3 genomes AF: 0.0669 AC: 10177 AN: 152056 Hom.: 424 Cov.: 32

Gnomad AFR AF: 0.0530

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0501

Gnomad ASJ AF: 0.0925

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.0261

Gnomad FIN AF: 0.0507

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0889

Gnomad OTH AF: 0.0733

GnomAD3 exomes AF: 0.0633 AC: 15900 AN: 251260 Hom.: 663 AF XY: 0.0631 AC XY: 8565 AN XY: 135780

Gnomad AFR exome AF: 0.0513

Gnomad AMR exome AF: 0.0342

Gnomad ASJ exome AF: 0.0938

Gnomad EAS exome AF: 0.000272

Gnomad SAS exome AF: 0.0279

Gnomad FIN exome AF: 0.0580

Gnomad NFE exome AF: 0.0909

Gnomad OTH exome AF: 0.0819

GnomAD4 exome AF: 0.0791 AC: 115648 AN: 1461314 Hom.: 5150 Cov.: 31 AF XY: 0.0781 AC XY: 56784 AN XY: 726922

Gnomad4 AFR exome AF: 0.0523

Gnomad4 AMR exome AF: 0.0365

Gnomad4 ASJ exome AF: 0.0920

Gnomad4 EAS exome AF: 0.000202

Gnomad4 SAS exome AF: 0.0294

Gnomad4 FIN exome AF: 0.0603

Gnomad4 NFE exome AF: 0.0892

Gnomad4 OTH exome AF: 0.0723

GnomAD4 genome AF: 0.0669 AC: 10177 AN: 152174 Hom.: 425 Cov.: 32 AF XY: 0.0635 AC XY: 4722 AN XY: 74382

Gnomad4 AFR AF: 0.0529

Gnomad4 AMR AF: 0.0500

Gnomad4 ASJ AF: 0.0925

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0259

Gnomad4 FIN AF: 0.0507

Gnomad4 NFE AF: 0.0889

Gnomad4 OTH AF: 0.0735

Alfa AF: 0.0812 Hom.: 698

Bravo AF: 0.0663

Asia WGS AF: 0.0160 AC: 56 AN: 3478

EpiCase AF: 0.0878

EpiControl AF: 0.0867

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	1.0
DANN	Benign	0.66

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: rs17293432; hg19: chr20-19565671; COSMIC: COSV60120240;