20-19545422-C-T

Variant names:

• chr20-19545422-C-T
• rs6081636
• NM_020689.4:c.348+29858C>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.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
• Publications: 5 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020689.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC24A3	NM_020689.4	MANE Select	c.348+29858C>T		intron	N/A	NP_065740.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC24A3	ENST00000328041.11	TSL:1 MANE Select	c.348+29858C>T		intron	N/A	ENSP00000333519.5	Q9HC58
	SLC24A3	ENST00000962751.1		c.348+29858C>T		intron	N/A	ENSP00000632810.1

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

African (AFR) AF: 0.116 AC: 4807 AN: 41532

American (AMR) AF: 0.160 AC: 2453 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1018 AN: 3468

East Asian (EAS) AF: 0.220 AC: 1139 AN: 5172

South Asian (SAS) AF: 0.193 AC: 929 AN: 4810

European-Finnish (FIN) AF: 0.292 AC: 3082 AN: 10572

Middle Eastern (MID) AF: 0.253 AC: 74 AN: 292

European-Non Finnish (NFE) AF: 0.251 AC: 17079 AN: 67994

Other (OTH) AF: 0.207 AC: 437 AN: 2112

Alfa AF: 0.212 Hom.: 2071

Bravo AF: 0.192

Asia WGS AF: 0.176 AC: 610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	14
DANN	Benign	0.74
PhyloP100		0.54
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: rs6081636; hg19: chr20-19526066;