rs990097

Positions:

• chr20-19308327-T-C

Variant summary

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

The NM_020689.4(SLC24A3):​c.271+27240T>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 152,222 control chromosomes in the GnomAD database, including 4,491 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 (4491 hom., cov: 33)
• Consequence: SLC24A3 NM_020689.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC24A3	NM_020689.4	c.271+27240T>C		intron_variant		ENST00000328041.11	NP_065740.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC24A3	ENST00000328041.11	c.271+27240T>C		intron_variant		1	NM_020689.4	ENSP00000333519	P1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23571 AN: 152104 Hom.: 4475 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: 0.274

Gnomad SAS AF: 0.0613

Gnomad FIN AF: 0.0200

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: 23647 AN: 152222 Hom.: 4491 Cov.: 33 AF XY: 0.156 AC XY: 11642 AN XY: 74442

Gnomad4 AFR AF: 0.429

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.273

Gnomad4 SAS AF: 0.0611

Gnomad4 FIN AF: 0.0200

Gnomad4 NFE AF: 0.00632

Gnomad4 OTH AF: 0.126

Alfa AF: 0.0897 Hom.: 327

Bravo AF: 0.184

Asia WGS AF: 0.203 AC: 704 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	3.0
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs990097; hg19: chr20-19288971;