20-19277749-T-C

Variant names:

• chr20-19277749-T-C
• rs3790171
• NM_020689.4:c.143-3210T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_020689.4(SLC24A3):​c.143-3210T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,236 control chromosomes in the GnomAD database, including 2,091 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 0.16 (2091 hom., cov: 33)
• Consequence: SLC24A3 NM_020689.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.95
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC24A3	NM_020689.4	c.143-3210T>C		intron_variant	Intron 1 of 16	ENST00000328041.11	NP_065740.2
SLC24A3-AS1	NR_024564.1	n.529+5390A>G		intron_variant	Intron 2 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC24A3	ENST00000328041.11	c.143-3210T>C		intron_variant	Intron 1 of 16	1	NM_020689.4	ENSP00000333519.5
SLC24A3-AS1	ENST00000319682.2	n.529+5390A>G		intron_variant	Intron 2 of 7	2

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24500 AN: 152118 Hom.: 2088 Cov.: 33

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.0982

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.161 AC: 24520 AN: 152236 Hom.: 2091 Cov.: 33 AF XY: 0.162 AC XY: 12043 AN XY: 74436

African (AFR) AF: 0.151 AC: 6295 AN: 41556

American (AMR) AF: 0.150 AC: 2297 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0982 AC: 341 AN: 3472

East Asian (EAS) AF: 0.238 AC: 1231 AN: 5176

South Asian (SAS) AF: 0.155 AC: 748 AN: 4826

European-Finnish (FIN) AF: 0.198 AC: 2099 AN: 10590

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11029 AN: 67998

Other (OTH) AF: 0.159 AC: 337 AN: 2114

Alfa AF: 0.157 Hom.: 1384

Bravo AF: 0.159

Asia WGS AF: 0.187 AC: 650 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	16
DANN	Benign	0.82
PhyloP100		3.0
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: rs3790171; hg19: chr20-19258393;