dbSNP rs3790278: SLC24A3:p.Leu213Leu (chr20-19654088-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_020689.4(SLC24A3):c.639G>A(p.Leu213Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 1,607,002 control chromosomes in the GnomAD database, including 318,382 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 0.64 ( 31993 hom., cov: 30)

Exomes 𝑓: 0.62 ( 286389 hom. )

Consequence

SLC24A3
NM_020689.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.796

Publications

22 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP7

Synonymous conserved (PhyloP=0.796 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC24A3	NM_020689.4 link	c.639G>A	p.Leu213Leu	synonymous_variant	Exon 7 of 17	ENST00000328041.11	NP_065740.2	Q9HC58

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC24A3	ENST00000328041.11 link	c.639G>A	p.Leu213Leu	synonymous_variant	Exon 7 of 17	1	NM_020689.4	ENSP00000333519.5		Q9HC58

Frequencies

GnomAD3 genomes

AF:

0.641

AC:

97193

AN:

151652

Hom.:

31959

Cov.:

show subpopulations

Gnomad AFR

AF:

0.751

Gnomad AMI

AF:

0.734

Gnomad AMR

AF:

0.547

Gnomad ASJ

AF:

0.570

Gnomad EAS

AF:

0.265

Gnomad SAS

AF:

0.497

Gnomad FIN

AF:

0.633

Gnomad MID

AF:

0.566

Gnomad NFE

AF:

0.638

Gnomad OTH

AF:

0.618

GnomAD2 exomes

AF:

0.577

AC:

144321

AN:

250230

AF XY:

0.576

show subpopulations

Gnomad AFR exome

AF:

0.754

Gnomad AMR exome

AF:

0.493

Gnomad ASJ exome

AF:

0.571

Gnomad EAS exome

AF:

0.253

Gnomad FIN exome

AF:

0.634

Gnomad NFE exome

AF:

0.637

Gnomad OTH exome

AF:

0.590

GnomAD4 exome

AF:

0.621

AC:

904356

AN:

1455232

Hom.:

286389

Cov.:

AF XY:

0.619

AC XY:

448227

AN XY:

724146

show subpopulations

African (AFR)

AF:

0.749

AC:

24967

AN:

33342

American (AMR)

AF:

0.504

AC:

22429

AN:

44498

Ashkenazi Jewish (ASJ)

AF:

0.570

AC:

14810

AN:

26000

East Asian (EAS)

AF:

0.275

AC:

10900

AN:

39654

South Asian (SAS)

AF:

0.510

AC:

43756

AN:

85852

European-Finnish (FIN)

AF:

0.639

AC:

34091

AN:

53324

Middle Eastern (MID)

AF:

0.579

AC:

3328

AN:

5752

European-Non Finnish (NFE)

AF:

0.645

AC:

714053

AN:

1106630

Other (OTH)

AF:

0.599

AC:

36022

AN:

60180

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.410

Heterozygous variant carriers

16519

33038

49556

66075

82594

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18636

37272

55908

74544

93180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.641

AC:

97278

AN:

151770

Hom.:

31993

Cov.:

AF XY:

0.632

AC XY:

46833

AN XY:

74150

show subpopulations

African (AFR)

AF:

0.751

AC:

31094

AN:

41376

American (AMR)

AF:

0.546

AC:

8328

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.570

AC:

1973

AN:

3462

East Asian (EAS)

AF:

0.265

AC:

1359

AN:

5128

South Asian (SAS)

AF:

0.497

AC:

2390

AN:

4806

European-Finnish (FIN)

AF:

0.633

AC:

6672

AN:

10534

Middle Eastern (MID)

AF:

0.544

AC:

160

AN:

294

European-Non Finnish (NFE)

AF:

0.638

AC:

43343

AN:

67910

Other (OTH)

AF:

0.614

AC:

1291

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1706

3412

5117

6823

8529

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

766

1532

2298

3064

3830

<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:

0.634

Hom.:

62775

Bravo

AF:

0.642

Asia WGS

AF:

0.410

AC:

1430

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

7.6

(source)

DANN

Benign

0.71

PhyloP100

0.80

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over