3-193414642-G-A

Position:

• chr3-193414642-G-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.2951C>T​(p.Ala984Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ATP13A4 NM_032279.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.182

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=0.11145803).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP13A4	NM_032279.4	c.2951C>T	p.Ala984Val	missense_variant	26/30	ENST00000342695.9
ATP13A4	XM_047449063.1	c.3080C>T	p.Ala1027Val	missense_variant	28/32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP13A4	ENST00000342695.9	c.2951C>T	p.Ala984Val	missense_variant	26/30	1	NM_032279.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251368 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135852

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461798 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727198

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	16
DANN	Benign	0.44
DEOGEN2	Benign	0.0094	T;T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	0.84	.;L
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.73	N;N
REVEL	Benign	0.22
Sift	Benign	0.40	T;T
Sift4G	Benign	0.61	T;T
Polyphen		0.0	.;B
Vest4		0.16
MutPred		0.52		.;Loss of helix (P = 0.079);
MVP		0.50
MPC		0.11
ClinPred		0.047	T
GERP RS		0.43
Varity_R		0.037
gMVP		0.44

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: rs1182325288; hg19: chr3-193132431;