chr20-19580020-G-A

Variant names:

• chr20-19580020-G-A
• rs3790261
• NM_020689.4:c.369G>A

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.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
• Publications: 27 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=-0.68).
• 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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC24A3	NM_020689.4	MANE Select	c.369G>A	p.Ala123Ala	synonymous	Exon 4 of 17	NP_065740.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC24A3	ENST00000328041.11	TSL:1 MANE Select	c.369G>A	p.Ala123Ala	synonymous	Exon 4 of 17	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

GnomAD2 exomes AF: 0.733 AC: 184130 AN: 251274 AF XY: 0.743

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 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

African (AFR) AF: 0.510 AC: 17027 AN: 33416

American (AMR) AF: 0.683 AC: 30505 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.790 AC: 20623 AN: 26116

East Asian (EAS) AF: 0.588 AC: 23339 AN: 39684

South Asian (SAS) AF: 0.764 AC: 65827 AN: 86168

European-Finnish (FIN) AF: 0.818 AC: 43654 AN: 53390

Middle Eastern (MID) AF: 0.761 AC: 4390 AN: 5766

European-Non Finnish (NFE) AF: 0.763 AC: 846695 AN: 1110006

Other (OTH) AF: 0.744 AC: 44899 AN: 60332

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

African (AFR) AF: 0.512 AC: 21175 AN: 41358

American (AMR) AF: 0.704 AC: 10748 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.784 AC: 2721 AN: 3470

East Asian (EAS) AF: 0.640 AC: 3300 AN: 5160

South Asian (SAS) AF: 0.752 AC: 3633 AN: 4828

European-Finnish (FIN) AF: 0.835 AC: 8841 AN: 10588

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.762 AC: 51835 AN: 67982

Other (OTH) AF: 0.716 AC: 1513 AN: 2112

Alfa AF: 0.736 Hom.: 81333

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.41
DANN	Benign	0.62
PhyloP100		-3.8
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: rs3790261; hg19: chr20-19560664; COSMIC: COSV60112137;