3-130996904-A-G

Variant names:

• chr3-130996904-A-G
• rs3773814
• NM_001378687.1:c.2243+108A>G

Variant summary

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

The NM_001378687.1(ATP2C1):​c.2243+108A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000151 in 662,128 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: ATP2C1 NM_001378687.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• 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: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Orphanet

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=-0.8).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378687.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2C1	NM_001378687.1	MANE Select	c.2243+108A>G		intron	N/A	NP_001365616.1
	ATP2C1	NM_001378511.1		c.2345+108A>G		intron	N/A	NP_001365440.1
	ATP2C1	NM_001199180.2		c.2345+108A>G		intron	N/A	NP_001186109.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2C1	ENST00000510168.6	TSL:5 MANE Select	c.2243+108A>G		intron	N/A	ENSP00000427461.1
	ATP2C1	ENST00000359644.7	TSL:1	c.2243+108A>G		intron	N/A	ENSP00000352665.3
	ATP2C1	ENST00000422190.6	TSL:1	c.2243+108A>G		intron	N/A	ENSP00000402677.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000151 AC: 1 AN: 662128 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 357578

African (AFR) AF: 0.00 AC: 0 AN: 17744

American (AMR) AF: 0.00 AC: 0 AN: 40818

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20676

East Asian (EAS) AF: 0.00 AC: 0 AN: 35814

South Asian (SAS) AF: 0.00 AC: 0 AN: 67532

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4182

European-Non Finnish (NFE) AF: 0.00000253 AC: 1 AN: 395788

Other (OTH) AF: 0.00 AC: 0 AN: 34186

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.3
DANN	Benign	0.77
PhyloP100		-1.4

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: rs3773814; hg19: chr3-130715748;