ENST00000328560:c.-237C>A

Variant names:

• chr3-130894533-C-A
• rs115940289
• ENST00000328560.12:c.-237C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000328560.12(ATP2C1):​c.-237C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,708 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 31)
• Consequence: ATP2C1 ENST00000328560.12 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.447
• Publications: 0 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: Orphanet, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000328560.12. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2C1	NM_001378687.1	MANE Select	c.-180-57C>A		intron	N/A	NP_001365616.1	P98194-1
	ATP2C1	NM_001378511.1		c.109-35883C>A		intron	N/A	NP_001365440.1
	ATP2C1	NM_001199180.2		c.109-35883C>A		intron	N/A	NP_001186109.1	P98194-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2C1	ENST00000328560.12	TSL:1	c.-237C>A		5_prime_UTR	Exon 1 of 27	ENSP00000329664.8	P98194-2
	ATP2C1	ENST00000510168.6	TSL:5 MANE Select	c.-180-57C>A		intron	N/A	ENSP00000427461.1	P98194-1
	ATP2C1	ENST00000513801.5	TSL:1	c.-43+196C>A		intron	N/A	ENSP00000422872.1	P98194-3

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151708 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151708 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74066

African (AFR) AF: 0.00 AC: 0 AN: 41280

American (AMR) AF: 0.00 AC: 0 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4734

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67924

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 5

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	14
DANN	Benign	0.90
PhyloP100		0.45
PromoterAI		-0.017	Neutral
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

Other links and lift over

dbSNP: rs115940289; hg19: chr3-130613377;