Genetic Variant NM_020689.4:c.369G>A (chr20-19580020-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.369G>A(p.Ala123Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 1,611,542 control chromosomes in the GnomAD database, including 451,913 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 0.69 ( 37162 hom., cov: 31)

Exomes 𝑓: 0.75 ( 414751 hom. )

Consequence

SLC24A3
NM_020689.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.76

Publications

27 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:

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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=-0.68).

BP7

Synonymous conserved (PhyloP=-3.76 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC24A3	NM_020689.4 link	c.369G>A	p.Ala123Ala	synonymous_variant	Exon 4 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.369G>A	p.Ala123Ala	synonymous_variant	Exon 4 of 17	1	NM_020689.4	ENSP00000333519.5		Q9HC58

Frequencies

GnomAD3 genomes

AF:

0.689

AC:

104688

AN:

151860

Hom.:

37165

Cov.:

show subpopulations

Gnomad AFR

AF:

0.512

Gnomad AMI

AF:

0.803

Gnomad AMR

AF:

0.704

Gnomad ASJ

AF:

0.784

Gnomad EAS

AF:

0.640

Gnomad SAS

AF:

0.751

Gnomad FIN

AF:

0.835

Gnomad MID

AF:

0.753

Gnomad NFE

AF:

0.763

Gnomad OTH

AF:

0.722

GnomAD2 exomes

AF:

0.733

AC:

184130

AN:

251274

AF XY:

0.743

show subpopulations

Gnomad AFR exome

AF:

0.504

Gnomad AMR exome

AF:

0.680

Gnomad ASJ exome

AF:

0.779

Gnomad EAS exome

AF:

0.654

Gnomad FIN exome

AF:

0.821

Gnomad NFE exome

AF:

0.764

Gnomad OTH exome

AF:

0.751

GnomAD4 exome

AF:

0.752

AC:

1096959

AN:

1459564

Hom.:

414751

Cov.:

AF XY:

0.753

AC XY:

547108

AN XY:

726190

show subpopulations

African (AFR)

AF:

0.510

AC:

17027

AN:

33416

American (AMR)

AF:

0.683

AC:

30505

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.790

AC:

20623

AN:

26116

East Asian (EAS)

AF:

0.588

AC:

23339

AN:

39684

South Asian (SAS)

AF:

0.764

AC:

65827

AN:

86168

European-Finnish (FIN)

AF:

0.818

AC:

43654

AN:

53390

Middle Eastern (MID)

AF:

0.761

AC:

4390

AN:

5766

European-Non Finnish (NFE)

AF:

0.763

AC:

846695

AN:

1110006

Other (OTH)

AF:

0.744

AC:

44899

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

13575

27150

40726

54301

67876

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20282

40564

60846

81128

101410

<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:

0.689

AC:

104717

AN:

151978

Hom.:

37162

Cov.:

AF XY:

0.695

AC XY:

51601

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.512

AC:

21175

AN:

41358

American (AMR)

AF:

0.704

AC:

10748

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.784

AC:

2721

AN:

3470

East Asian (EAS)

AF:

0.640

AC:

3300

AN:

5160

South Asian (SAS)

AF:

0.752

AC:

3633

AN:

4828

European-Finnish (FIN)

AF:

0.835

AC:

8841

AN:

10588

Middle Eastern (MID)

AF:

0.745

AC:

219

AN:

294

European-Non Finnish (NFE)

AF:

0.762

AC:

51835

AN:

67982

Other (OTH)

AF:

0.716

AC:

1513

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1591

3182

4774

6365

7956

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

822

1644

2466

3288

4110

<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:

0.736

Hom.:

81333

Bravo

AF:

0.671

Asia WGS

AF:

0.662

AC:

2305

AN:

3478

EpiCase

AF:

0.768

EpiControl

AF:

0.768

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.41

(source)

DANN

Benign

0.62

PhyloP100

-3.8

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

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