rs3790278

Positions:

• chr20-19654088-G-A
• chr20-19654088-G-C

Variant summary

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

The NM_020689.4(SLC24A3):​c.639G>A​(p.Leu213=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 1,607,002 control chromosomes in the GnomAD database, including 318,382 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 0.64 (31993 hom., cov: 30)
  • Exomes 𝑓: 0.62 (286389 hom.)
• Consequence: SLC24A3 NM_020689.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.796

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=-0.48).
• BP7: Synonymous conserved (PhyloP=0.796 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC24A3	NM_020689.4	c.639G>A	p.Leu213=	synonymous_variant	7/17	ENST00000328041.11	NP_065740.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC24A3	ENST00000328041.11	c.639G>A	p.Leu213=	synonymous_variant	7/17	1	NM_020689.4	ENSP00000333519	P1

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97193 AN: 151652 Hom.: 31959 Cov.: 30

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.618

GnomAD3 exomes AF: 0.577 AC: 144321 AN: 250230 Hom.: 43621 AF XY: 0.576 AC XY: 77890 AN XY: 135242

Gnomad AFR exome AF: 0.754

Gnomad AMR exome AF: 0.493

Gnomad ASJ exome AF: 0.571

Gnomad EAS exome AF: 0.253

Gnomad SAS exome AF: 0.508

Gnomad FIN exome AF: 0.634

Gnomad NFE exome AF: 0.637

Gnomad OTH exome AF: 0.590

GnomAD4 exome AF: 0.621 AC: 904356 AN: 1455232 Hom.: 286389 Cov.: 44 AF XY: 0.619 AC XY: 448227 AN XY: 724146

Gnomad4 AFR exome AF: 0.749

Gnomad4 AMR exome AF: 0.504

Gnomad4 ASJ exome AF: 0.570

Gnomad4 EAS exome AF: 0.275

Gnomad4 SAS exome AF: 0.510

Gnomad4 FIN exome AF: 0.639

Gnomad4 NFE exome AF: 0.645

Gnomad4 OTH exome AF: 0.599

GnomAD4 genome AF: 0.641 AC: 97278 AN: 151770 Hom.: 31993 Cov.: 30 AF XY: 0.632 AC XY: 46833 AN XY: 74150

Gnomad4 AFR AF: 0.751

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.570

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.497

Gnomad4 FIN AF: 0.633

Gnomad4 NFE AF: 0.638

Gnomad4 OTH AF: 0.614

Alfa AF: 0.633 Hom.: 48094

Bravo AF: 0.642

Asia WGS AF: 0.410 AC: 1430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	7.6
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3790278; hg19: chr20-19634732; COSMIC: COSV60120812;