3-130946687-A-G

Position:

• chr3-130946687-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378687.1(ATP2C1):​c.531+4988A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,254 control chromosomes in the GnomAD database, including 2,525 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 0.18 (2525 hom., cov: 32)
• Consequence: ATP2C1 NM_001378687.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.52

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP2C1	NM_001378687.1	c.531+4988A>G		intron_variant		ENST00000510168.6	NP_001365616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP2C1	ENST00000510168.6	c.531+4988A>G		intron_variant		5	NM_001378687.1	ENSP00000427461	P3

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26797 AN: 152136 Hom.: 2525 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.0449

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.176 AC: 26808 AN: 152254 Hom.: 2525 Cov.: 32 AF XY: 0.170 AC XY: 12682 AN XY: 74458

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.0449

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.190

Alfa AF: 0.188 Hom.: 1361

Bravo AF: 0.179

Asia WGS AF: 0.120 AC: 418 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.13
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs2669858; hg19: chr3-130665531; COSMIC: COSV60754408;