Genetic Variant SLC24A3:c.143-25713C>T (chr20-19255246-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020689.4(SLC24A3):c.143-25713C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,272 control chromosomes in the GnomAD database, including 1,149 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 0.11 ( 1149 hom., cov: 32)

Consequence

SLC24A3
NM_020689.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.04

Publications

2 publications found

Variant links:

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 links:

SLC24A3-AS1 (HGNC:40540): (SLC24A3 antisense RNA 1)

SLC24A3-AS1 links:

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new If you want to explore the variant's impact on the transcript NM_020689.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.151 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.143-25713C>T		intron	N/A	NP_065740.2
	SLC24A3-AS1	NR_024564.1		n.1104+2383G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC24A3	ENST00000328041.11	TSL:1 MANE Select	c.143-25713C>T	intron	N/A	ENSP00000333519.5	Q9HC58
SLC24A3	ENST00000962751.1		c.143-25713C>T	intron	N/A	ENSP00000632810.1
SLC24A3-AS1	ENST00000319682.2	TSL:2	n.1104+2383G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.107

AC:

16353

AN:

152154

Hom.:

1149

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0295

Gnomad AMI

AF:

0.186

Gnomad AMR

AF:

0.0942

Gnomad ASJ

AF:

0.0784

Gnomad EAS

AF:

0.0584

Gnomad SAS

AF:

0.0736

Gnomad FIN

AF:

0.181

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.154

Gnomad OTH

AF:

0.100

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

GnomAD4 genome

AF:

0.107

AC:

16362

AN:

152272

Hom.:

1149

Cov.:

AF XY:

0.108

AC XY:

8048

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.0296

AC:

1229

AN:

41586

American (AMR)

AF:

0.0941

AC:

1440

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0784

AC:

272

AN:

3470

East Asian (EAS)

AF:

0.0586

AC:

303

AN:

5174

South Asian (SAS)

AF:

0.0735

AC:

354

AN:

4818

European-Finnish (FIN)

AF:

0.181

AC:

1913

AN:

10592

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.154

AC:

10454

AN:

68004

Other (OTH)

AF:

0.102

AC:

216

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

733

1466

2198

2931

3664

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

174

348

522

696

870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.133

Hom.:

843

Bravo

AF:

0.0974

Asia WGS

AF:

0.0800

AC:

279

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.71

(source)

DANN

Benign

0.56

PhyloP100

-1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over