20-19365540-T-C

Variant names:

• chr20-19365540-T-C
• rs6046024
• NM_020689.4:c.271+84453T>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.271+84453T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,130 control chromosomes in the GnomAD database, including 9,046 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 0.23 (9046 hom., cov: 32)
• Consequence: SLC24A3 NM_020689.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.119
• Publications: 4 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC24A3	NM_020689.4	c.271+84453T>C		intron_variant	Intron 2 of 16	ENST00000328041.11	NP_065740.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC24A3	ENST00000328041.11	c.271+84453T>C		intron_variant	Intron 2 of 16	1	NM_020689.4	ENSP00000333519.5

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34116 AN: 152012 Hom.: 9002 Cov.: 32

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.0367

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0338

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0225

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.225 AC: 34231 AN: 152130 Hom.: 9046 Cov.: 32 AF XY: 0.224 AC XY: 16678 AN XY: 74386

African (AFR) AF: 0.622 AC: 25766 AN: 41426

American (AMR) AF: 0.244 AC: 3732 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0367 AC: 127 AN: 3462

East Asian (EAS) AF: 0.334 AC: 1729 AN: 5174

South Asian (SAS) AF: 0.111 AC: 536 AN: 4826

European-Finnish (FIN) AF: 0.0338 AC: 359 AN: 10614

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0225 AC: 1532 AN: 68012

Other (OTH) AF: 0.187 AC: 396 AN: 2114

Alfa AF: 0.106 Hom.: 9733

Bravo AF: 0.261

Asia WGS AF: 0.257 AC: 893 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.1
DANN	Benign	0.83
PhyloP100		0.12
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: rs6046024; hg19: chr20-19346184;