rs74437357

Positions:

chr3-193334980-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The ENST00000342358.9(ATP13A5):c.1063C>T(p.Gln355Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0293 in 1,613,820 control chromosomes in the GnomAD database, including 863 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.023 ( 42 hom., cov: 32)

Exomes 𝑓: 0.030 ( 821 hom. )

Consequence

ATP13A5
ENST00000342358.9 stop_gained

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 9.68

Variant links:

Genes affected

ATP13A5 (HGNC:31789): (ATPase 13A5) This gene encodes a member of the P5 subfamily of P-type transport ATPases. P-type ATPases form a large superfamily of cation and lipid pumps that transport inorganic cations and other substrates across cell membranes. P5 ATPases are localized to membranes of the endoplasmic reticulum (ER) and serve many important functions including transport of cargo proteins to the Golgi, glycosylation and cell wall biosynthesis, control of protein insertion orientation, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) degradation, and sensitivity to unfolded protein response (UPR) activators. The encoded protein is organized into three cytoplasmic domains (A, P, and N) and two membrane-embedded domains (T and S). The N-domain binds ATP and serves as a built-in protein kinase, which phosphorylates the P-domain. The A-domain is an intrinsic protein phosphatase, which dephosphorylates the P-domain once during each catalytic cycle. [provided by RefSeq, Jul 2017]

ATP13A5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 3-193334980-G-A is Benign according to our data. Variant chr3-193334980-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 402400.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-193334980-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0231 (3512/152282) while in subpopulation NFE AF= 0.0337 (2291/68016). AF 95% confidence interval is 0.0325. There are 42 homozygotes in gnomad4. There are 1750 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 42 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ATP13A5	NM_198505.4 linkuse as main transcript	c.1063C>T	p.Gln355Ter	stop_gained	10/30	ENST00000342358.9	NP_940907.2
ATP13A5	XM_011512770.3 linkuse as main transcript	c.1063C>T	p.Gln355Ter	stop_gained	10/27		XP_011511072.1
ATP13A5	XM_047448075.1 linkuse as main transcript	c.19-3669C>T		intron_variant			XP_047304031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP13A5	ENST00000342358.9 linkuse as main transcript	c.1063C>T	p.Gln355Ter	stop_gained	10/30	1	NM_198505.4	ENSP00000341942	P1

Frequencies

GnomAD3 genomes

AF:

0.0231

AC:

3512

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00557

Gnomad AMI

AF:

0.0527

Gnomad AMR

AF:

0.0206

Gnomad ASJ

AF:

0.0110

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00559

Gnomad FIN

AF:

0.0498

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0337

Gnomad OTH

AF:

0.0158

GnomAD3 exomes

AF:

0.0220

AC:

5520

AN:

251162

Hom.:

AF XY:

0.0219

AC XY:

2968

AN XY:

135732

show subpopulations

Gnomad AFR exome

AF:

0.00499

Gnomad AMR exome

AF:

0.00926

Gnomad ASJ exome

AF:

0.00784

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00644

Gnomad FIN exome

AF:

0.0491

Gnomad NFE exome

AF:

0.0322

Gnomad OTH exome

AF:

0.0206

GnomAD4 exome

AF:

0.0299

AC:

43716

AN:

1461538

Hom.:

821

Cov.:

AF XY:

0.0291

AC XY:

21166

AN XY:

727052

show subpopulations

Gnomad4 AFR exome

AF:

0.00514

Gnomad4 AMR exome

AF:

0.00859

Gnomad4 ASJ exome

AF:

0.00834

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00665

Gnomad4 FIN exome

AF:

0.0480

Gnomad4 NFE exome

AF:

0.0343

Gnomad4 OTH exome

AF:

0.0267

GnomAD4 genome

AF:

0.0231

AC:

3512

AN:

152282

Hom.:

Cov.:

AF XY:

0.0235

AC XY:

1750

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00556

Gnomad4 AMR

AF:

0.0205

Gnomad4 ASJ

AF:

0.0110

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00560

Gnomad4 FIN

AF:

0.0498

Gnomad4 NFE

AF:

0.0337

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.0292

Hom.:

106

Bravo

AF:

0.0201

TwinsUK

AF:

0.0418

AC:

155

ALSPAC

AF:

0.0361

AC:

139

ESP6500AA

AF:

0.00545

AC:

ESP6500EA

AF:

0.0298

AC:

256

ExAC

AF:

0.0217

AC:

2633

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.0307

EpiControl

AF:

0.0282

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC frequency -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.66

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Pathogenic

1.2

Eigen_PC

Pathogenic

1.1

FATHMM_MKL

Pathogenic

0.99

MutationTaster

Benign

1.0

Vest4

0.35

GERP RS

5.9

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over