Variant chr3-193275045-CA-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_198505.4(ATP13A5):c.3653delT(p.Leu1218fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000621 in 1,614,074 control chromosomes in the GnomAD database, including 14 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00064 ( 14 hom. )

Consequence

ATP13A5
NM_198505.4 frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.99

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:

PLAAT1 (HGNC:14922): (phospholipase A and acyltransferase 1) Enables acyltransferase activity, transferring groups other than amino-acyl groups and phospholipase activity. Involved in N-acylphosphatidylethanolamine metabolic process and phosphatidylcholine metabolic process. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

PLAAT1 links:

ATP13A5 (HGNC:):

ATP13A5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 3-193275045-CA-C is Benign according to our data. Variant chr3-193275045-CA-C is described in ClinVar as [Benign]. Clinvar id is 783316.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000638 (933/1461770) while in subpopulation AMR AF= 0.0204 (913/44700). AF 95% confidence interval is 0.0193. There are 14 homozygotes in gnomad4_exome. There are 353 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP13A5	NM_198505.4 linkuse as main transcript	c.3653delT	p.Leu1218fs	frameshift_variant	30/30	ENST00000342358.9	NP_940907.2	Q4VNC0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ATP13A5	ENST00000342358.9 linkuse as main transcript	c.3653delT	p.Leu1218fs	frameshift_variant	30/30	1	NM_198505.4	ENSP00000341942.4	Q4VNC0
ATP13A5	ENST00000495496.1 linkuse as main transcript	n.1475delT		non_coding_transcript_exon_variant	12/12	5
PLAAT1	ENST00000416012.1 linkuse as main transcript	n.*60-2590delA		intron_variant		5		ENSP00000414431.1	H7C3Y1

Frequencies

GnomAD3 genomes

AF:

0.000460

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00452

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00328

AC:

823

AN:

251260

Hom.:

AF XY:

0.00222

AC XY:

301

AN XY:

135790

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0235

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.000638

AC:

933

AN:

1461770

Hom.:

Cov.:

AF XY:

0.000485

AC XY:

353

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.0204

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

AF:

0.000453

AC:

AN:

152304

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00445

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000136

Hom.:

Bravo

AF:

0.00144

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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