rs6136651

Positions:

• chr20-19215452-G-A
• chr20-19215452-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020689.4(SLC24A3):​c.142+2468G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0798 in 152,062 control chromosomes in the GnomAD database, including 1,982 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 0.080 (1982 hom., cov: 32)
• Consequence: SLC24A3 NM_020689.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.512

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC24A3	NM_020689.4	c.142+2468G>A		intron_variant		ENST00000328041.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC24A3	ENST00000328041.11	c.142+2468G>A		intron_variant		1	NM_020689.4	P1

Frequencies

GnomAD3 genomes AF: 0.0796 AC: 12094 AN: 151944 Hom.: 1979 Cov.: 32

Gnomad AFR AF: 0.0865

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.0618

Gnomad FIN AF: 0.0593

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00706

Gnomad OTH AF: 0.0675

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

GnomAD4 genome AF: 0.0798 AC: 12128 AN: 152062 Hom.: 1982 Cov.: 32 AF XY: 0.0879 AC XY: 6536 AN XY: 74324

Gnomad4 AFR AF: 0.0867

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.00634

Gnomad4 EAS AF: 0.705

Gnomad4 SAS AF: 0.0621

Gnomad4 FIN AF: 0.0593

Gnomad4 NFE AF: 0.00706

Gnomad4 OTH AF: 0.0716

Alfa AF: 0.0110 Hom.: 6

Bravo AF: 0.0990

Asia WGS AF: 0.339 AC: 1177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.2
DANN	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs6136651; hg19: chr20-19196096;