rs13076493

Variant names:

• chr3-131011673-C-T
• rs13076493
• ENST00000359644.7:c.2755-4479C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000359644.7(ATP2C1):​c.2755-4479C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,112 control chromosomes in the GnomAD database, including 3,816 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (3816 hom., cov: 32)
• Consequence: ATP2C1 ENST00000359644.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.181
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• Hailey-Hailey disease

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2C1	NM_001378511.1	c.2857-4479C>T		intron_variant	Intron 27 of 27		NP_001365440.1
ATP2C1	NM_001199180.2	c.2827-4479C>T		intron_variant	Intron 27 of 27		NP_001186109.1
ATP2C1	NM_001001486.2	c.2755-4479C>T		intron_variant	Intron 28 of 28		NP_001001486.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2C1	ENST00000359644.7	c.2755-4479C>T		intron_variant	Intron 27 of 27	1		ENSP00000352665.3
ATP2C1	ENST00000422190.6	c.2725-4479C>T		intron_variant	Intron 27 of 27	1		ENSP00000402677.2
ATP2C1	ENST00000513801.5	c.2677-4479C>T		intron_variant	Intron 27 of 27	1		ENSP00000422872.1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33187 AN: 151994 Hom.: 3813 Cov.: 32

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.221

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.218 AC: 33219 AN: 152112 Hom.: 3816 Cov.: 32 AF XY: 0.212 AC XY: 15730 AN XY: 74350

African (AFR) AF: 0.277 AC: 11501 AN: 41478

American (AMR) AF: 0.158 AC: 2419 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 752 AN: 3472

East Asian (EAS) AF: 0.118 AC: 611 AN: 5178

South Asian (SAS) AF: 0.220 AC: 1059 AN: 4820

European-Finnish (FIN) AF: 0.149 AC: 1579 AN: 10574

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14479 AN: 67994

Other (OTH) AF: 0.222 AC: 468 AN: 2108

Alfa AF: 0.218 Hom.: 1464

Bravo AF: 0.223

Asia WGS AF: 0.181 AC: 633 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.9
DANN	Benign	0.48
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13076493; hg19: chr3-130730517; COSMIC: COSV53908000; COSMIC: COSV53908000;