chr3-193402758-G-A

Position:

• chr3-193402758-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000342695.9(ATP13A4):​c.3485C>T​(p.Pro1162Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATP13A4 ENST00000342695.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.33

Genes affected

ATP13A4 (HGNC:25422): (ATPase 13A4) Predicted to enable ATPase-coupled cation transmembrane transporter activity. Predicted to be involved in cellular calcium ion homeostasis. Predicted to be located in endoplasmic reticulum membrane and endosome membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22689992).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP13A4	NM_032279.4	c.3485C>T	p.Pro1162Leu	missense_variant	30/30	ENST00000342695.9	NP_115655.2
ATP13A4	XM_047449063.1	c.3614C>T	p.Pro1205Leu	missense_variant	32/32		XP_047305019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP13A4	ENST00000342695.9	c.3485C>T	p.Pro1162Leu	missense_variant	30/30	1	NM_032279.4	ENSP00000339182	P1

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

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2021

The c.3485C>T (p.P1162L) alteration is located in exon 30 (coding exon 30) of the ATP13A4 gene. This alteration results from a C to T substitution at nucleotide position 3485, causing the proline (P) at amino acid position 1162 to be replaced by a leucine (L). 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	0.077
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.077	.;T;T
Eigen	Benign	-0.026
Eigen_PC	Benign	0.062
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.5	.;.;M
MutationTaster	Benign	0.59	D;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-5.2	D;D;D
REVEL	Benign	0.18
Sift	Benign	0.052	T;D;D
Sift4G	Uncertain	0.047	D;D;D
Polyphen		0.33	.;.;B
Vest4		0.17
MutPred		0.42		.;.;Gain of catalytic residue at P1162 (P = 0.003);
MVP		0.64
MPC		0.15
ClinPred		0.96	D
GERP RS		4.1
Varity_R		0.22
gMVP		0.28

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: chr3-193120547;