rs3790278

Variant names:

• chr20-19654088-G-A
• rs3790278
• NM_020689.4:c.639G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_020689.4(SLC24A3):​c.639G>A​(p.Leu213Leu) 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
• Publications: 22 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020689.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC24A3	NM_020689.4	MANE Select	c.639G>A	p.Leu213Leu	synonymous	Exon 7 of 17	NP_065740.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC24A3	ENST00000328041.11	TSL:1 MANE Select	c.639G>A	p.Leu213Leu	synonymous	Exon 7 of 17	ENSP00000333519.5	Q9HC58
	SLC24A3	ENST00000962751.1		c.564G>A	p.Leu188Leu	synonymous	Exon 6 of 15	ENSP00000632810.1

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

GnomAD2 exomes AF: 0.577 AC: 144321 AN: 250230 AF XY: 0.576

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 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

African (AFR) AF: 0.749 AC: 24967 AN: 33342

American (AMR) AF: 0.504 AC: 22429 AN: 44498

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 14810 AN: 26000

East Asian (EAS) AF: 0.275 AC: 10900 AN: 39654

South Asian (SAS) AF: 0.510 AC: 43756 AN: 85852

European-Finnish (FIN) AF: 0.639 AC: 34091 AN: 53324

Middle Eastern (MID) AF: 0.579 AC: 3328 AN: 5752

European-Non Finnish (NFE) AF: 0.645 AC: 714053 AN: 1106630

Other (OTH) AF: 0.599 AC: 36022 AN: 60180

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

African (AFR) AF: 0.751 AC: 31094 AN: 41376

American (AMR) AF: 0.546 AC: 8328 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1973 AN: 3462

East Asian (EAS) AF: 0.265 AC: 1359 AN: 5128

South Asian (SAS) AF: 0.497 AC: 2390 AN: 4806

European-Finnish (FIN) AF: 0.633 AC: 6672 AN: 10534

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.638 AC: 43343 AN: 67910

Other (OTH) AF: 0.614 AC: 1291 AN: 2104

Alfa AF: 0.634 Hom.: 62775

Bravo AF: 0.642

Asia WGS AF: 0.410 AC: 1430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	7.6
DANN	Benign	0.71
PhyloP100		0.80
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3790278; hg19: chr20-19634732; COSMIC: COSV60120812;