20-19654103-T-C

Variant names:

• chr20-19654103-T-C
• rs3790279
• NM_020689.4:c.654T>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.654T>C​(p.Ile218Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 1,608,674 control chromosomes in the GnomAD database, including 317,053 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 0.63 (31248 hom., cov: 30)
  • Exomes 𝑓: 0.62 (285805 hom.)
• Consequence: SLC24A3 NM_020689.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160
• Publications: 23 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=-0.51).
• BP7: Synonymous conserved (PhyloP=0.016 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.72 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.654T>C	p.Ile218Ile	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.654T>C	p.Ile218Ile	synonymous	Exon 7 of 17	ENSP00000333519.5
	SLC24A3	ENST00000962751.1		c.579T>C	p.Ile193Ile	synonymous	Exon 6 of 15	ENSP00000632810.1

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96238 AN: 151752 Hom.: 31217 Cov.: 30

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.616

GnomAD2 exomes AF: 0.575 AC: 143964 AN: 250322 AF XY: 0.575

Gnomad AFR exome AF: 0.728

Gnomad AMR exome AF: 0.492

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: 904381 AN: 1456804 Hom.: 285805 Cov.: 46 AF XY: 0.618 AC XY: 448289 AN XY: 724872

African (AFR) AF: 0.721 AC: 24049 AN: 33372

American (AMR) AF: 0.503 AC: 22407 AN: 44508

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 14818 AN: 26014

East Asian (EAS) AF: 0.275 AC: 10922 AN: 39672

South Asian (SAS) AF: 0.510 AC: 43824 AN: 85942

European-Finnish (FIN) AF: 0.639 AC: 34101 AN: 53342

Middle Eastern (MID) AF: 0.578 AC: 3323 AN: 5748

European-Non Finnish (NFE) AF: 0.645 AC: 714959 AN: 1107952

Other (OTH) AF: 0.597 AC: 35978 AN: 60254

GnomAD4 genome AF: 0.634 AC: 96320 AN: 151870 Hom.: 31248 Cov.: 30 AF XY: 0.625 AC XY: 46384 AN XY: 74190

African (AFR) AF: 0.726 AC: 30073 AN: 41396

American (AMR) AF: 0.546 AC: 8333 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1977 AN: 3464

East Asian (EAS) AF: 0.265 AC: 1364 AN: 5144

South Asian (SAS) AF: 0.497 AC: 2389 AN: 4806

European-Finnish (FIN) AF: 0.634 AC: 6682 AN: 10534

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.638 AC: 43384 AN: 67958

Other (OTH) AF: 0.612 AC: 1291 AN: 2110

Alfa AF: 0.630 Hom.: 20051

Bravo AF: 0.635

Asia WGS AF: 0.409 AC: 1426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	7.5
DANN	Benign	0.76
PhyloP100		0.016
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
SpliceAI score (max)		0.010		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: rs3790279; hg19: chr20-19634747; COSMIC: COSV60112148;