Genetic Variant NM_001367549.1:c.3403-147G>C (chr3-194413986-C-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001367549.1(ATP13A3):c.3403-147G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 667,842 control chromosomes in the GnomAD database, including 9,820 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.19 ( 4642 hom., cov: 32)

Exomes 𝑓: 0.11 ( 5178 hom. )

Consequence

ATP13A3
NM_001367549.1 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.237

Publications

2 publications found

Variant links:

Genes affected

ATP13A3 (HGNC:24113): (ATPase 13A3) ATP13A3 is a member of the P-type ATPase family of proteins that transport a variety of cations across membranes. Other P-type ATPases include ATP7B (MIM 606882) and ATP7A (MIM 300011).[supplied by OMIM, Aug 2008]

ATP13A3 Gene-Disease associations (from GenCC):

pulmonary arterial hypertension
Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen

ATP13A3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 3-194413986-C-G is Benign according to our data. Variant chr3-194413986-C-G is described in ClinVar as Benign. ClinVar VariationId is 1288959.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367549.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATP13A3	NM_001367549.1	MANE Select	c.3403-147G>C	intron	N/A	NP_001354478.1	A0A2R8Y635
ATP13A3	NM_001374836.1		c.3322-147G>C	intron	N/A	NP_001361765.1
ATP13A3	NM_001437993.1		c.3403-147G>C	intron	N/A	NP_001424922.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATP13A3	ENST00000645319.2	MANE Select	c.3403-147G>C	intron	N/A	ENSP00000494937.2	A0A2R8Y635
ATP13A3	ENST00000429136.7	TSL:1	n.1249-147G>C	intron	N/A
ATP13A3	ENST00000461660.2	TSL:1	n.507-147G>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.190

AC:

28915

AN:

151846

Hom.:

4626

Cov.:

show subpopulations

Gnomad AFR

AF:

0.433

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.141

Gnomad ASJ

AF:

0.0829

Gnomad EAS

AF:

0.206

Gnomad SAS

AF:

0.243

Gnomad FIN

AF:

0.0853

Gnomad MID

AF:

0.134

Gnomad NFE

AF:

0.0741

Gnomad OTH

AF:

0.177

GnomAD4 exome

AF:

0.111

AC:

57284

AN:

515876

Hom.:

5178

AF XY:

0.115

AC XY:

31360

AN XY:

273838

show subpopulations

African (AFR)

AF:

0.436

AC:

6186

AN:

14198

American (AMR)

AF:

0.126

AC:

3521

AN:

27948

Ashkenazi Jewish (ASJ)

AF:

0.0744

AC:

1159

AN:

15568

East Asian (EAS)

AF:

0.207

AC:

6592

AN:

31828

South Asian (SAS)

AF:

0.228

AC:

11462

AN:

50298

European-Finnish (FIN)

AF:

0.0765

AC:

2478

AN:

32378

Middle Eastern (MID)

AF:

0.123

AC:

340

AN:

2760

European-Non Finnish (NFE)

AF:

0.0705

AC:

22033

AN:

312718

Other (OTH)

AF:

0.125

AC:

3513

AN:

28180

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

2143

4287

6430

8574

10717

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

376

752

1128

1504

1880

<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:

0.191

AC:

28972

AN:

151966

Hom.:

4642

Cov.:

AF XY:

0.190

AC XY:

14135

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.434

AC:

17945

AN:

41376

American (AMR)

AF:

0.141

AC:

2150

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.0829

AC:

288

AN:

3472

East Asian (EAS)

AF:

0.206

AC:

1066

AN:

5168

South Asian (SAS)

AF:

0.243

AC:

1167

AN:

4812

European-Finnish (FIN)

AF:

0.0853

AC:

900

AN:

10552

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0741

AC:

5041

AN:

68004

Other (OTH)

AF:

0.174

AC:

368

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1014

2028

3042

4056

5070

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

282

564

846

1128

1410

<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:

0.0373

Hom.:

Bravo

AF:

0.204

Asia WGS

AF:

0.245

AC:

851

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.4

(source)

DANN

Benign

0.42

PhyloP100

-0.24

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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