Genetic Variant ATP13A4:c.738+139A>G (chr3-193489591-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_032279.4(ATP13A4):c.738+139A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 834,050 control chromosomes in the GnomAD database, including 71,508 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 0.43 ( 14384 hom., cov: 32)

Exomes 𝑓: 0.41 ( 57124 hom. )

Consequence

ATP13A4
NM_032279.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00400

Publications

18 publications found

Variant links:

Genes affected

ATP13A4 (HGNC:25422): (ATPase 13A4) Predicted to enable ATPase-coupled cation transmembrane transporter activity. Predicted to be involved in cellular calcium ion homeostasis. Predicted to be located in endoplasmic reticulum membrane and endosome membrane. [provided by Alliance of Genome Resources, Apr 2022]

ATP13A4 links:

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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=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032279.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP13A4	NM_032279.4	MANE Select	c.738+139A>G		intron	N/A	NP_115655.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ATP13A4	ENST00000342695.9	TSL:1 MANE Select	c.738+139A>G	intron	N/A	ENSP00000339182.4
ATP13A4	ENST00000490925.5	TSL:1	n.846+139A>G	intron	N/A
ATP13A4	ENST00000392443.7	TSL:5	c.738+139A>G	intron	N/A	ENSP00000376238.3

Frequencies

GnomAD3 genomes

AF:

0.432

AC:

65647

AN:

151872

Hom.:

14368

Cov.:

show subpopulations

Gnomad AFR

AF:

0.506

Gnomad AMI

AF:

0.377

Gnomad AMR

AF:

0.479

Gnomad ASJ

AF:

0.362

Gnomad EAS

AF:

0.438

Gnomad SAS

AF:

0.450

Gnomad FIN

AF:

0.348

Gnomad MID

AF:

0.456

Gnomad NFE

AF:

0.393

Gnomad OTH

AF:

0.422

GnomAD4 exome

AF:

0.406

AC:

277172

AN:

682060

Hom.:

57124

AF XY:

0.406

AC XY:

146869

AN XY:

361654

show subpopulations

African (AFR)

AF:

0.512

AC:

8885

AN:

17344

American (AMR)

AF:

0.512

AC:

16620

AN:

32476

Ashkenazi Jewish (ASJ)

AF:

0.368

AC:

6207

AN:

16882

East Asian (EAS)

AF:

0.409

AC:

14215

AN:

34724

South Asian (SAS)

AF:

0.445

AC:

26261

AN:

59060

European-Finnish (FIN)

AF:

0.342

AC:

14134

AN:

41306

Middle Eastern (MID)

AF:

0.427

AC:

1024

AN:

2400

European-Non Finnish (NFE)

AF:

0.396

AC:

176238

AN:

444594

Other (OTH)

AF:

0.408

AC:

13588

AN:

33274

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

8100

16201

24301

32402

40502

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3184

6368

9552

12736

15920

<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:

0.432

AC:

65706

AN:

151990

Hom.:

14384

Cov.:

AF XY:

0.431

AC XY:

32005

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.506

AC:

20985

AN:

41434

American (AMR)

AF:

0.479

AC:

7317

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.362

AC:

1257

AN:

3468

East Asian (EAS)

AF:

0.438

AC:

2261

AN:

5162

South Asian (SAS)

AF:

0.451

AC:

2169

AN:

4814

European-Finnish (FIN)

AF:

0.348

AC:

3676

AN:

10572

Middle Eastern (MID)

AF:

0.456

AC:

134

AN:

294

European-Non Finnish (NFE)

AF:

0.393

AC:

26686

AN:

67964

Other (OTH)

AF:

0.418

AC:

879

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1864

3728

5591

7455

9319

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

602

1204

1806

2408

3010

<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:

0.423

Hom.:

10662

Bravo

AF:

0.445

Asia WGS

AF:

0.457

AC:

1590

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.5

(source)

DANN

Benign

0.54

PhyloP100

-0.0040

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over