20-19656698-C-T

Position:

• chr20-19656698-C-T

Variant summary

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

The NM_020689.4(SLC24A3):​c.687+2562C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 151,998 control chromosomes in the GnomAD database, including 31,448 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 (31448 hom., cov: 31)
• Consequence: SLC24A3 NM_020689.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC24A3	NM_020689.4	c.687+2562C>T		intron_variant		ENST00000328041.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC24A3	ENST00000328041.11	c.687+2562C>T		intron_variant		1	NM_020689.4	P1

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96954 AN: 151878 Hom.: 31416 Cov.: 31

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.645

Gnomad OTH AF: 0.620

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

GnomAD4 genome AF: 0.638 AC: 97040 AN: 151998 Hom.: 31448 Cov.: 31 AF XY: 0.632 AC XY: 46936 AN XY: 74304

Gnomad4 AFR AF: 0.709

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.584

Gnomad4 EAS AF: 0.378

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.654

Gnomad4 NFE AF: 0.645

Gnomad4 OTH AF: 0.617

Alfa AF: 0.633 Hom.: 14812

Bravo AF: 0.636

Asia WGS AF: 0.459 AC: 1597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.7
DANN	Benign	0.63

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: rs4813368; hg19: chr20-19637342;