Variant 3-130850882-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001378511.1(ATP2C1):c.62T>A(p.Ile21Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000288 in 1,424,734 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0015 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00015 ( 2 hom. )

Consequence

ATP2C1
NM_001378511.1 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.89

Variant links:

Genes affected

ATP2C1 (HGNC:13211): (ATPase secretory pathway Ca2+ transporting 1) The protein encoded by this gene belongs to the family of P-type cation transport ATPases. This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium ions. Defects in this gene cause Hailey-Hailey disease, an autosomal dominant disorder. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]

ATP2C1 links:

LOC107986023 (HGNC:):

LOC107986023 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010445058).

BP6

Variant 3-130850882-T-A is Benign according to our data. Variant chr3-130850882-T-A is described in ClinVar as [Benign]. Clinvar id is 3035209.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00146 (222/152326) while in subpopulation AFR AF= 0.005 (208/41560). AF 95% confidence interval is 0.00445. There are 2 homozygotes in gnomad4. There are 100 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 222 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
ATP2C1	NM_001378511.1 link	c.62T>A	p.Ile21Asn	missense_variant	1/28	NP_001365440.1
ATP2C1	NM_001199180.2 link	c.62T>A	p.Ile21Asn	missense_variant	1/28	NP_001186109.1	P98194-7
ATP2C1	NM_001199181.3 link	c.62T>A	p.Ile21Asn	missense_variant	1/27	NP_001186110.1	P98194B4E2Q0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	UniProt
ATP2C1	ENST00000507488.6 link	c.62T>A	p.Ile21Asn	missense_variant	1/28	2	ENSP00000421326.3	P98194-7
ATP2C1	ENST00000505330.5 link	c.62T>A	p.Ile21Asn	missense_variant	1/27	2	ENSP00000423774.2	B4E2Q0
ATP2C1	ENST00000504381.5 link	c.62T>A	p.Ile21Asn	missense_variant	1/27	2	ENSP00000425320.2	P98194-8
ATP2C1	ENST00000509150.1 link	n.100T>A		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes

AF:

0.00147

AC:

223

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00504

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

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:

0.0000294

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000180

AC:

AN:

61204

Hom.:

AF XY:

0.000141

AC XY:

AN XY:

35470

show subpopulations

Gnomad AFR exome

AF:

0.00407

Gnomad AMR exome

AF:

0.000226

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:

0.0000400

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000149

AC:

189

AN:

1272408

Hom.:

Cov.:

AF XY:

0.000141

AC XY:

AN XY:

624140

show subpopulations

Gnomad4 AFR exome

AF:

0.00561

Gnomad4 AMR exome

AF:

0.000445

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:

0.00000292

Gnomad4 OTH exome

AF:

0.000529

GnomAD4 genome

AF:

0.00146

AC:

222

AN:

152326

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

100

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00500

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000898

Hom.:

Bravo

AF:

0.00177

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ATP2C1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 19, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0074

T;.;.

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.058

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.79

T;T;T

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.010

T;T;T

MetaSVM

Benign

-0.35

PrimateAI

Uncertain

0.63

PROVEAN

Benign

0.28

N;N;N

Sift

Benign

0.44

T;D;T

Sift4G

Benign

0.31

T;D;T

Polyphen

0.0020

B;.;.

Vest4

0.54

MVP

0.75

ClinPred

0.044

GERP RS

6.0

gMVP

0.35

Splicing

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