Genetic Variant ATP13A3:p.Val1126Phe (chr3-194419905-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001367549.1(ATP13A3):c.3376G>T(p.Val1126Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ATP13A3
NM_001367549.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.30

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25579056).

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	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP13A3	NM_001367549.1	MANE Select	c.3376G>T	p.Val1126Phe	missense	Exon 31 of 34	NP_001354478.1	A0A2R8Y635
ATP13A3	NM_001374836.1		c.3295G>T	p.Val1099Phe	missense	Exon 30 of 33	NP_001361765.1
ATP13A3	NM_001437993.1		c.3376G>T	p.Val1126Phe	missense	Exon 31 of 33	NP_001424922.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP13A3	ENST00000645319.2	MANE Select	c.3376G>T	p.Val1126Phe	missense	Exon 31 of 34	ENSP00000494937.2	A0A2R8Y635
ATP13A3	ENST00000429136.7	TSL:1	n.1222G>T		non_coding_transcript_exon	Exon 10 of 13
ATP13A3	ENST00000461660.2	TSL:1	n.480G>T		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1407124

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

699606

African (AFR)

AF:

0.00

AC:

AN:

29884

American (AMR)

AF:

0.00

AC:

AN:

28396

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24134

East Asian (EAS)

AF:

0.00

AC:

AN:

37822

South Asian (SAS)

AF:

0.00

AC:

AN:

75124

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52690

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5606

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1095578

Other (OTH)

AF:

0.00

AC:

AN:

57890

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Pathogenic

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.28

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.85

M_CAP

Benign

0.029

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.59

MutationAssessor

Benign

1.2

PhyloP100

1.3

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.87

REVEL

Uncertain

0.42

Sift

Benign

0.41

Sift4G

Benign

0.65

Polyphen

0.0

Vest4

0.63

MutPred

0.54

Loss of catalytic residue at V1126 (P = 0.0955)

MVP

0.92

MPC

0.48

ClinPred

0.51

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

0.97

Varity_R

0.096

gMVP

0.70

Mutation Taster

=80/20

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over