Variant 3-130930437-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The NM_001378687.1(ATP2C1):c.28C>T(p.Pro10Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000089 in 1,460,020 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000089 ( 0 hom. )

Consequence

ATP2C1
NM_001378687.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.99

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), ATP2C1. . Trascript score misZ 3.7693 (greater than threshold 3.09). GenCC has associacion of gene with Hailey-Hailey disease.

BP4

Computational evidence support a benign effect (MetaRNN=0.20333752).

BS2

High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP2C1	NM_001378687.1 linkuse as main transcript	c.28C>T	p.Pro10Ser	missense_variant	3/28	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.28C>T	p.Pro10Ser	missense_variant	3/28	5	NM_001378687.1	ENSP00000427461	P3	P98194-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

251036

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135694

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000882

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00000890

AC:

AN:

1460020

Hom.:

Cov.:

AF XY:

0.00000964

AC XY:

AN XY:

726438

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000829

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2021

The c.28C>T (p.P10S) alteration is located in exon 2 (coding exon 2) of the ATP2C1 gene. This alteration results from a C to T substitution at nucleotide position 28, causing the proline (P) at amino acid position 10 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0046

T;.;.;T;T;.;T;.;.;T;.;.

Eigen

Benign

-0.20

Eigen_PC

Benign

0.018

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.95

D;D;D;.;.;D;D;D;.;D;D;D

M_CAP

Uncertain

0.098

MetaRNN

Benign

0.20

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.23

MutationAssessor

Benign

1.6

.;.;.;L;L;L;.;.;L;L;L;L

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.12

.;.;.;N;N;.;N;N;N;N;N;N

REVEL

Benign

0.25

Sift

Uncertain

0.027

.;.;.;D;D;.;D;D;D;D;D;D

Sift4G

Benign

0.29

T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.027

B;.;.;B;B;B;.;.;B;B;.;B

Vest4

0.42

MutPred

0.43

.;.;.;Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);

MVP

0.65

ClinPred

0.23

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.060

gMVP

0.31

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