3-130930853-A-G

Position:

• chr3-130930853-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001378687.1(ATP2C1):​c.117+327A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0365 in 152,240 control chromosomes in the GnomAD database, including 159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.037 (159 hom., cov: 32)
• Consequence: ATP2C1 NM_001378687.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.173

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 3-130930853-A-G is Benign according to our data. Variant chr3-130930853-A-G is described in ClinVar as [Benign]. Clinvar id is 1270134.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP2C1	NM_001378687.1	c.117+327A>G		intron_variant		ENST00000510168.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP2C1	ENST00000510168.6	c.117+327A>G		intron_variant		5	NM_001378687.1	P3

Frequencies

GnomAD3 genomes AF: 0.0365 AC: 5559 AN: 152122 Hom.: 158 Cov.: 32

Gnomad AFR AF: 0.00924

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0422

Gnomad ASJ AF: 0.0343

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0582

Gnomad FIN AF: 0.0369

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0522

Gnomad OTH AF: 0.0469

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

GnomAD4 genome AF: 0.0365 AC: 5559 AN: 152240 Hom.: 159 Cov.: 32 AF XY: 0.0359 AC XY: 2671 AN XY: 74436

Gnomad4 AFR AF: 0.00924

Gnomad4 AMR AF: 0.0421

Gnomad4 ASJ AF: 0.0343

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0584

Gnomad4 FIN AF: 0.0369

Gnomad4 NFE AF: 0.0522

Gnomad4 OTH AF: 0.0459

Alfa AF: 0.0414 Hom.: 28

Bravo AF: 0.0344

Asia WGS AF: 0.0210 AC: 74 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 21, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	5.2
DANN	Benign	0.86

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: rs864072; hg19: chr3-130649697;