20-19590937-G-C

Variant names:

• chr20-19590937-G-C
• rs3790268
• NM_020689.4:c.612+5393G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020689.4(SLC24A3):​c.612+5393G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,166 control chromosomes in the GnomAD database, including 1,644 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 0.14 (1644 hom., cov: 32)
• Consequence: SLC24A3 NM_020689.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.185
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC24A3	NM_020689.4	c.612+5393G>C		intron_variant	Intron 6 of 16	ENST00000328041.11	NP_065740.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC24A3	ENST00000328041.11	c.612+5393G>C		intron_variant	Intron 6 of 16	1	NM_020689.4	ENSP00000333519.5

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21515 AN: 152048 Hom.: 1644 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.0286

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0932

Gnomad SAS AF: 0.0725

Gnomad FIN AF: 0.0771

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.128

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.141 AC: 21520 AN: 152166 Hom.: 1644 Cov.: 32 AF XY: 0.137 AC XY: 10177 AN XY: 74424

African (AFR) AF: 0.191 AC: 7939 AN: 41498

American (AMR) AF: 0.111 AC: 1701 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 477 AN: 3470

East Asian (EAS) AF: 0.0938 AC: 486 AN: 5180

South Asian (SAS) AF: 0.0721 AC: 348 AN: 4826

European-Finnish (FIN) AF: 0.0771 AC: 818 AN: 10612

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9415 AN: 67978

Other (OTH) AF: 0.129 AC: 272 AN: 2114

Alfa AF: 0.124 Hom.: 708

Bravo AF: 0.146

Asia WGS AF: 0.0840 AC: 292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.2
DANN	Benign	0.39
PhyloP100		-0.18
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: rs3790268; hg19: chr20-19571581;