Variant 3-130894533-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000328560.12(ATP2C1):c.-237C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00652 in 1,393,578 control chromosomes in the GnomAD database, including 355 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.029 ( 205 hom., cov: 31)

Exomes 𝑓: 0.0038 ( 150 hom. )

Consequence

ATP2C1
ENST00000328560.12 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.447

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP2C1	NM_001378687.1 linkuse as main transcript	c.-180-57C>T		intron_variant		ENST00000510168.6	NP_001365616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP2C1	ENST00000510168.6 linkuse as main transcript	c.-180-57C>T		intron_variant		5	NM_001378687.1	ENSP00000427461	P3	P98194-1

Frequencies

GnomAD3 genomes

AF:

0.0291

AC:

4420

AN:

151686

Hom.:

204

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0961

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0142

Gnomad ASJ

AF:

0.0248

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000845

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00138

Gnomad OTH

AF:

0.0235

GnomAD4 exome

AF:

0.00376

AC:

4670

AN:

1241778

Hom.:

150

Cov.:

AF XY:

0.00348

AC XY:

2086

AN XY:

599900

show subpopulations

Gnomad4 AFR exome

AF:

0.0963

Gnomad4 AMR exome

AF:

0.0116

Gnomad4 ASJ exome

AF:

0.0223

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000453

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000904

Gnomad4 OTH exome

AF:

0.00915

GnomAD4 genome

AF:

0.0291

AC:

4423

AN:

151800

Hom.:

205

Cov.:

AF XY:

0.0288

AC XY:

2133

AN XY:

74174

show subpopulations

Gnomad4 AFR

AF:

0.0959

Gnomad4 AMR

AF:

0.0141

Gnomad4 ASJ

AF:

0.0248

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000634

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.00138

Gnomad4 OTH

AF:

0.0232

Alfa

AF:

0.000743

Hom.:

Bravo

AF:

0.0329

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Familial benign pemphigus

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.96

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.4

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