3-130930496-A-C

Variant names:

• chr3-130930496-A-C
• NM_001378687.1:c.87A>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001378687.1(ATP2C1):​c.87A>C​(p.Leu29Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATP2C1 NM_001378687.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.22

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2C1	NM_001378687.1	c.87A>C	p.Leu29Phe	missense_variant	Exon 3 of 28	ENST00000510168.6	NP_001365616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2C1	ENST00000510168.6	c.87A>C	p.Leu29Phe	missense_variant	Exon 3 of 28	5	NM_001378687.1	ENSP00000427461.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Feb 18, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.87A>C (p.L29F) alteration is located in exon 2 (coding exon 2) of the ATP2C1 gene. This alteration results from a A to C substitution at nucleotide position 87, causing the leucine (L) at amino acid position 29 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.078	T;.;.;T;T;.;.;.;T;.;.;T;.;.;T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.96	D;D;D;.;.;D;D;D;D;D;.;D;D;D;D
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.63	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.74	D
MutationAssessor	Uncertain	2.6	.;.;.;M;M;M;.;.;.;.;M;M;M;M;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.7	.;.;.;N;N;.;N;N;N;N;N;N;N;N;N
REVEL	Uncertain	0.51
Sift	Benign	0.11	.;.;.;T;T;.;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.093	T;T;T;T;T;T;T;T;T;D;T;T;T;T;T
Polyphen		0.43	B;.;.;B;B;B;.;.;.;.;B;B;.;B;.
Vest4		0.55
MutPred		0.54		.;.;.;Gain of glycosylation at S32 (P = 0.0469);Gain of glycosylation at S32 (P = 0.0469);Gain of glycosylation at S32 (P = 0.0469);.;.;Gain of glycosylation at S32 (P = 0.0469);Gain of glycosylation at S32 (P = 0.0469);Gain of glycosylation at S32 (P = 0.0469);Gain of glycosylation at S32 (P = 0.0469);Gain of glycosylation at S32 (P = 0.0469);Gain of glycosylation at S32 (P = 0.0469);.;
MVP		0.76
ClinPred		0.92	D
GERP RS		5.8
Varity_R		0.11
gMVP		0.51

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-130649340;