20-19255246-C-T

Variant names:

• chr20-19255246-C-T
• rs1012646
• NM_020689.4:c.143-25713C>T

Variant summary

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

The NM_020689.4(SLC24A3):​c.143-25713C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,272 control chromosomes in the GnomAD database, including 1,149 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 0.11 (1149 hom., cov: 32)
• Consequence: SLC24A3 NM_020689.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 2 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]

SLC24A3-AS1 (HGNC:40540): (SLC24A3 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC24A3	NM_020689.4	c.143-25713C>T		intron_variant	Intron 1 of 16	ENST00000328041.11	NP_065740.2
SLC24A3-AS1	NR_024564.1	n.1104+2383G>A		intron_variant	Intron 6 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC24A3	ENST00000328041.11	c.143-25713C>T		intron_variant	Intron 1 of 16	1	NM_020689.4	ENSP00000333519.5
SLC24A3-AS1	ENST00000319682.2	n.1104+2383G>A		intron_variant	Intron 6 of 7	2

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16353 AN: 152154 Hom.: 1149 Cov.: 32

Gnomad AFR AF: 0.0295

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.0942

Gnomad ASJ AF: 0.0784

Gnomad EAS AF: 0.0584

Gnomad SAS AF: 0.0736

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.100

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

GnomAD4 genome AF: 0.107 AC: 16362 AN: 152272 Hom.: 1149 Cov.: 32 AF XY: 0.108 AC XY: 8048 AN XY: 74444

African (AFR) AF: 0.0296 AC: 1229 AN: 41586

American (AMR) AF: 0.0941 AC: 1440 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0784 AC: 272 AN: 3470

East Asian (EAS) AF: 0.0586 AC: 303 AN: 5174

South Asian (SAS) AF: 0.0735 AC: 354 AN: 4818

European-Finnish (FIN) AF: 0.181 AC: 1913 AN: 10592

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10454 AN: 68004

Other (OTH) AF: 0.102 AC: 216 AN: 2116

Alfa AF: 0.133 Hom.: 843

Bravo AF: 0.0974

Asia WGS AF: 0.0800 AC: 279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.71
DANN	Benign	0.56
PhyloP100		-1.0
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: rs1012646; hg19: chr20-19235890;