Genetic Variant NM_020689.4:c.480G>A (chr20-19585027-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.480G>A(p.Ser160Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.078 in 1,613,488 control chromosomes in the GnomAD database, including 5,575 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 0.067 ( 425 hom., cov: 32)

Exomes 𝑓: 0.079 ( 5150 hom. )

Consequence

SLC24A3
NM_020689.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.58

Publications

9 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=-0.61).

BP7

Synonymous conserved (PhyloP=-3.58 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.087 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC24A3	NM_020689.4 link	c.480G>A	p.Ser160Ser	synonymous_variant	Exon 5 of 17	ENST00000328041.11	NP_065740.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC24A3	ENST00000328041.11 link	c.480G>A	p.Ser160Ser	synonymous_variant	Exon 5 of 17	1	NM_020689.4	ENSP00000333519.5

Frequencies

GnomAD3 genomes

AF:

0.0669

AC:

10177

AN:

152056

Hom.:

424

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0530

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0501

Gnomad ASJ

AF:

0.0925

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.0261

Gnomad FIN

AF:

0.0507

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.0889

Gnomad OTH

AF:

0.0733

GnomAD2 exomes

AF:

0.0633

AC:

15900

AN:

251260

AF XY:

0.0631

show subpopulations

Gnomad AFR exome

AF:

0.0513

Gnomad AMR exome

AF:

0.0342

Gnomad ASJ exome

AF:

0.0938

Gnomad EAS exome

AF:

0.000272

Gnomad FIN exome

AF:

0.0580

Gnomad NFE exome

AF:

0.0909

Gnomad OTH exome

AF:

0.0819

GnomAD4 exome

AF:

0.0791

AC:

115648

AN:

1461314

Hom.:

5150

Cov.:

AF XY:

0.0781

AC XY:

56784

AN XY:

726922

show subpopulations

African (AFR)

AF:

0.0523

AC:

1750

AN:

33468

American (AMR)

AF:

0.0365

AC:

1633

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0920

AC:

2404

AN:

26128

East Asian (EAS)

AF:

0.000202

AC:

AN:

39692

South Asian (SAS)

AF:

0.0294

AC:

2539

AN:

86232

European-Finnish (FIN)

AF:

0.0603

AC:

3220

AN:

53404

Middle Eastern (MID)

AF:

0.101

AC:

583

AN:

5766

European-Non Finnish (NFE)

AF:

0.0892

AC:

99148

AN:

1111536

Other (OTH)

AF:

0.0723

AC:

4363

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

5215

10430

15644

20859

26074

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3562

7124

10686

14248

17810

<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:

0.0669

AC:

10177

AN:

152174

Hom.:

425

Cov.:

AF XY:

0.0635

AC XY:

4722

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.0529

AC:

2195

AN:

41530

American (AMR)

AF:

0.0500

AC:

765

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0925

AC:

321

AN:

3470

East Asian (EAS)

AF:

0.000387

AC:

AN:

5162

South Asian (SAS)

AF:

0.0259

AC:

125

AN:

4818

European-Finnish (FIN)

AF:

0.0507

AC:

538

AN:

10608

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0889

AC:

6041

AN:

67968

Other (OTH)

AF:

0.0735

AC:

155

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

478

957

1435

1914

2392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

224

336

448

560

<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:

0.0798

Hom.:

833

Bravo

AF:

0.0663

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.0878

EpiControl

AF:

0.0867

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

1.0

(source)

DANN

Benign

0.66

PhyloP100

-3.6

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