3-193407377-A-T

Variant names:

• chr3-193407377-A-T
• NM_032279.4:c.3314T>A

Variant summary

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

The NM_032279.4(ATP13A4):​c.3314T>A​(p.Val1105Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1105I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATP13A4 NM_032279.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.272

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=0.2504925).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP13A4	NM_032279.4	c.3314T>A	p.Val1105Asp	missense_variant	Exon 29 of 30	ENST00000342695.9	NP_115655.2
ATP13A4	XM_047449063.1	c.3443T>A	p.Val1148Asp	missense_variant	Exon 31 of 32		XP_047305019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP13A4	ENST00000342695.9	c.3314T>A	p.Val1105Asp	missense_variant	Exon 29 of 30	1	NM_032279.4	ENSP00000339182.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3314T>A (p.V1105D) alteration is located in exon 29 (coding exon 29) of the ATP13A4 gene. This alteration results from a T to A substitution at nucleotide position 3314, causing the valine (V) at amino acid position 1105 to be replaced by an aspartic acid (D). 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	0.14
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	11
DANN	Benign	0.79
DEOGEN2	Benign	0.0040	.;T;T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.81	T;T;T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.0	.;.;M
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.5	D;N;N
REVEL	Uncertain	0.38
Sift	Uncertain	0.026	D;T;T
Sift4G	Uncertain	0.011	D;T;T
Polyphen		0.024	.;.;B
Vest4		0.50
MutPred		0.63		.;.;Gain of loop (P = 0.069);
MVP		0.51
MPC		0.21
ClinPred		0.093	T
GERP RS		1.6
Varity_R		0.13
gMVP		0.38

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: chr3-193125166;