rs3790261

Positions:

• chr20-19580020-G-A
• chr20-19580020-G-C
• chr20-19580020-G-T

Variant summary

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

The NM_020689.4(SLC24A3):​c.369G>A​(p.Ala123Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 1,611,542 control chromosomes in the GnomAD database, including 451,913 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 0.69 (37162 hom., cov: 31)
  • Exomes 𝑓: 0.75 (414751 hom.)
• Consequence: SLC24A3 NM_020689.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.76

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=-0.68).
• BP7: Synonymous conserved (PhyloP=-3.76 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC24A3	NM_020689.4	c.369G>A	p.Ala123Ala	synonymous_variant	4/17	ENST00000328041.11	NP_065740.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC24A3	ENST00000328041.11	c.369G>A	p.Ala123Ala	synonymous_variant	4/17	1	NM_020689.4	ENSP00000333519.5

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104688 AN: 151860 Hom.: 37165 Cov.: 31

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.803

Gnomad AMR AF: 0.704

Gnomad ASJ AF: 0.784

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.751

Gnomad FIN AF: 0.835

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.722

GnomAD3 exomes AF: 0.733 AC: 184130 AN: 251274 Hom.: 68176 AF XY: 0.743 AC XY: 100868 AN XY: 135792

Gnomad AFR exome AF: 0.504

Gnomad AMR exome AF: 0.680

Gnomad ASJ exome AF: 0.779

Gnomad EAS exome AF: 0.654

Gnomad SAS exome AF: 0.765

Gnomad FIN exome AF: 0.821

Gnomad NFE exome AF: 0.764

Gnomad OTH exome AF: 0.751

GnomAD4 exome AF: 0.752 AC: 1096959 AN: 1459564 Hom.: 414751 Cov.: 40 AF XY: 0.753 AC XY: 547108 AN XY: 726190

Gnomad4 AFR exome AF: 0.510

Gnomad4 AMR exome AF: 0.683

Gnomad4 ASJ exome AF: 0.790

Gnomad4 EAS exome AF: 0.588

Gnomad4 SAS exome AF: 0.764

Gnomad4 FIN exome AF: 0.818

Gnomad4 NFE exome AF: 0.763

Gnomad4 OTH exome AF: 0.744

GnomAD4 genome AF: 0.689 AC: 104717 AN: 151978 Hom.: 37162 Cov.: 31 AF XY: 0.695 AC XY: 51601 AN XY: 74298

Gnomad4 AFR AF: 0.512

Gnomad4 AMR AF: 0.704

Gnomad4 ASJ AF: 0.784

Gnomad4 EAS AF: 0.640

Gnomad4 SAS AF: 0.752

Gnomad4 FIN AF: 0.835

Gnomad4 NFE AF: 0.762

Gnomad4 OTH AF: 0.716

Alfa AF: 0.743 Hom.: 67500

Bravo AF: 0.671

Asia WGS AF: 0.662 AC: 2305 AN: 3478

EpiCase AF: 0.768

EpiControl AF: 0.768

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.41
DANN	Benign	0.62

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: rs3790261; hg19: chr20-19560664; COSMIC: COSV60112137;