rs721488

Variant names:

• chr20-19317956-C-T
• rs721488
• NM_020689.4:c.271+36869C>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.271+36869C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0404 in 152,328 control chromosomes in the GnomAD database, including 503 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 0.040 (503 hom., cov: 33)
• Consequence: SLC24A3 NM_020689.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.504
• Publications: 0 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC24A3	NM_020689.4	c.271+36869C>T		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+36869C>T		intron_variant	Intron 2 of 16	1	NM_020689.4	ENSP00000333519.5

Frequencies

GnomAD3 genomes AF: 0.0404 AC: 6143 AN: 152210 Hom.: 500 Cov.: 33

Gnomad AFR AF: 0.0325

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.0571

Gnomad FIN AF: 0.0200

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00492

Gnomad OTH AF: 0.0392

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

GnomAD4 genome AF: 0.0404 AC: 6161 AN: 152328 Hom.: 503 Cov.: 33 AF XY: 0.0446 AC XY: 3320 AN XY: 74480

African (AFR) AF: 0.0326 AC: 1356 AN: 41574

American (AMR) AF: 0.164 AC: 2507 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3472

East Asian (EAS) AF: 0.266 AC: 1377 AN: 5178

South Asian (SAS) AF: 0.0572 AC: 276 AN: 4828

European-Finnish (FIN) AF: 0.0200 AC: 212 AN: 10620

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00492 AC: 335 AN: 68036

Other (OTH) AF: 0.0388 AC: 82 AN: 2112

Alfa AF: 0.0227 Hom.: 25

Bravo AF: 0.0533

Asia WGS AF: 0.165 AC: 570 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.20
PhyloP100		-0.50
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: rs721488; hg19: chr20-19298600;