3-130850713-T-A

Variant names:

• chr3-130850713-T-A
• rs1316658
• NM_001378511.1:c.-108T>A

Variant summary

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

The NM_001378511.1(ATP2C1):​c.-108T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATP2C1 NM_001378511.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105
• Publications: 12 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

ENSG00000306101 (HGNC:):

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=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378511.1. 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_001378511.1		c.-108T>A		5_prime_UTR	Exon 1 of 28	NP_001365440.1
	ATP2C1	NM_001199180.2		c.-108T>A		5_prime_UTR	Exon 1 of 28	NP_001186109.1	P98194-7
	ATP2C1	NM_001199181.3		c.-108T>A		5_prime_UTR	Exon 1 of 27	NP_001186110.1	B4E2Q0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2C1	ENST00000507488.6	TSL:2	c.-108T>A		5_prime_UTR	Exon 1 of 28	ENSP00000421326.3	P98194-7
	ATP2C1	ENST00000505330.5	TSL:2	c.-108T>A		5_prime_UTR	Exon 1 of 27	ENSP00000423774.2	B4E2Q0
	ATP2C1	ENST00000504381.5	TSL:2	c.-108T>A		5_prime_UTR	Exon 1 of 27	ENSP00000425320.2	P98194-8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 356206 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 185150

African (AFR) AF: 0.00 AC: 0 AN: 8642

American (AMR) AF: 0.00 AC: 0 AN: 10194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11366

East Asian (EAS) AF: 0.00 AC: 0 AN: 24306

South Asian (SAS) AF: 0.00 AC: 0 AN: 23266

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26262

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3278

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 227448

Other (OTH) AF: 0.00 AC: 0 AN: 21444

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.9
DANN	Benign	0.40
PhyloP100		0.10
PromoterAI		-0.020	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1316658; hg19: chr3-130569557;