20-19545422-C-T

Variant summary

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

The NM_020689.4(SLC24A3):c.348+29858C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,166 control chromosomes in the GnomAD database, including 3,572 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 0.21 (3572 hom., cov: 32)
• Consequence: SLC24A3 NM_020689.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.543

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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC24A3	NM_020689.4	c.348+29858C>T		intron_variant		ENST00000328041.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC24A3	ENST00000328041.11	c.348+29858C>T		intron_variant		1	NM_020689.4	P1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31261 AN: 152048 Hom.: 3571 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.205 AC: 31264 AN: 152166 Hom.: 3572 Cov.: 32 AF XY: 0.207 AC XY: 15392 AN XY: 74372

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.207

Alfa AF: 0.210 Hom.: 1860

Bravo AF: 0.192

Asia WGS AF: 0.176 AC: 610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	14
Dann	Benign	0.74

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: rs6081636; hg19: chr20-19526066;