rs990096

chr20-19308250-G-Cchr20-19308250-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020689.4(SLC24A3):c.271+27163G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,172 control chromosomes in the GnomAD database, including 4,481 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 (4481 hom., cov: 33)
• Consequence: SLC24A3 NM_020689.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.664

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC24A3	NM_020689.4	c.271+27163G>C		intron_variant		ENST00000328041.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC24A3	ENST00000328041.11	c.271+27163G>C		intron_variant		1	NM_020689.4	P1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23549 AN: 152054 Hom.: 4465 Cov.: 33

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.0615

Gnomad FIN AF: 0.0201

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00632

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.155 AC: 23625 AN: 152172 Hom.: 4481 Cov.: 33 AF XY: 0.156 AC XY: 11627 AN XY: 74424

Gnomad4 AFR AF: 0.429

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.0613

Gnomad4 FIN AF: 0.0201

Gnomad4 NFE AF: 0.00632

Gnomad4 OTH AF: 0.126

Alfa AF: 0.0896 Hom.: 325

Bravo AF: 0.184

Asia WGS AF: 0.201 AC: 697 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	4.0
Dann	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs990096; hg19: chr20-19288894;