rs2424234

Variant names:

• chr20-19383335-T-C
• rs2424234
• NM_020689.4:c.271+102248T>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+102248T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,210 control chromosomes in the GnomAD database, including 1,181 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 0.10 (1181 hom., cov: 32)
• Consequence: SLC24A3 NM_020689.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.575
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020689.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC24A3	NM_020689.4	MANE Select	c.271+102248T>C		intron	N/A	NP_065740.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC24A3	ENST00000328041.11	TSL:1 MANE Select	c.271+102248T>C		intron	N/A	ENSP00000333519.5

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15888 AN: 152092 Hom.: 1181 Cov.: 32

Gnomad AFR AF: 0.0242

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.0863

Gnomad ASJ AF: 0.0950

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.0948

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

GnomAD4 genome AF: 0.104 AC: 15884 AN: 152210 Hom.: 1181 Cov.: 32 AF XY: 0.107 AC XY: 7928 AN XY: 74404

African (AFR) AF: 0.0242 AC: 1004 AN: 41558

American (AMR) AF: 0.0865 AC: 1322 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0950 AC: 330 AN: 3472

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5178

South Asian (SAS) AF: 0.121 AC: 585 AN: 4828

European-Finnish (FIN) AF: 0.223 AC: 2364 AN: 10584

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9928 AN: 67988

Other (OTH) AF: 0.0929 AC: 196 AN: 2110

Alfa AF: 0.124 Hom.: 3063

Bravo AF: 0.0876

Asia WGS AF: 0.0510 AC: 177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.46
DANN	Benign	0.42
PhyloP100		-0.57
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: rs2424234; hg19: chr20-19363979;