chr3-130930702-T-C

Variant names:

• chr3-130930702-T-C
• rs77557042
• NM_001378687.1:c.117+176T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001378687.1(ATP2C1):​c.117+176T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0269 in 152,256 control chromosomes in the GnomAD database, including 190 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.027 (190 hom., cov: 32)
• Consequence: ATP2C1 NM_001378687.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.01
• Publications: 1 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 3-130930702-T-C is Benign according to our data. Variant chr3-130930702-T-C is described in ClinVar as Benign. ClinVar VariationId is 1236415.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0908 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2C1	NM_001378687.1	MANE Select	c.117+176T>C		intron	N/A	NP_001365616.1	P98194-1
	ATP2C1	NM_001378511.1		c.219+176T>C		intron	N/A	NP_001365440.1
	ATP2C1	NM_001199180.2		c.219+176T>C		intron	N/A	NP_001186109.1	P98194-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2C1	ENST00000510168.6	TSL:5 MANE Select	c.117+176T>C		intron	N/A	ENSP00000427461.1	P98194-1
	ATP2C1	ENST00000359644.7	TSL:1	c.117+176T>C		intron	N/A	ENSP00000352665.3	P98194-9
	ATP2C1	ENST00000422190.6	TSL:1	c.117+176T>C		intron	N/A	ENSP00000402677.2	P98194-5

Frequencies

GnomAD3 genomes AF: 0.0269 AC: 4099 AN: 152138 Hom.: 191 Cov.: 32

Gnomad AFR AF: 0.0935

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00865

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.0225

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

GnomAD4 genome AF: 0.0269 AC: 4102 AN: 152256 Hom.: 190 Cov.: 32 AF XY: 0.0250 AC XY: 1859 AN XY: 74464

African (AFR) AF: 0.0933 AC: 3874 AN: 41538

American (AMR) AF: 0.00871 AC: 133 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00432 AC: 15 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10630

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000441 AC: 30 AN: 67998

Other (OTH) AF: 0.0222 AC: 47 AN: 2114

Alfa AF: 0.0262 Hom.: 16

Bravo AF: 0.0314

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.3
DANN	Benign	0.72
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism

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: rs77557042; hg19: chr3-130649546;