chr3-193412297-T-C

Position:

• chr3-193412297-T-C

Variant summary

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

The NM_032279.4(ATP13A4):​c.3089A>G​(p.Asn1030Ser) 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. 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)
• Consequence: ATP13A4 NM_032279.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.462

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=0.104251534).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP13A4	NM_032279.4	c.3089A>G	p.Asn1030Ser	missense_variant	27/30	ENST00000342695.9
ATP13A4	XM_047449063.1	c.3218A>G	p.Asn1073Ser	missense_variant	29/32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP13A4	ENST00000342695.9	c.3089A>G	p.Asn1030Ser	missense_variant	27/30	1	NM_032279.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Nov 12, 2021

The c.3089A>G (p.N1030S) alteration is located in exon 27 (coding exon 27) of the ATP13A4 gene. This alteration results from a A to G substitution at nucleotide position 3089, causing the asparagine (N) at amino acid position 1030 to be replaced by a serine (S). 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	0.059
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	2.9
DANN	Benign	0.65
DEOGEN2	Benign	0.016	.;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.58	T;T;T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.6	.;.;L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.096
Sift	Benign	0.094	T;T;T
Sift4G	Benign	0.38	T;T;T
Polyphen		0.0030	.;.;B
Vest4		0.19
MutPred		0.38		.;.;Gain of glycosylation at S1029 (P = 0.0443);
MVP		0.47
MPC		0.090
ClinPred		0.11	T
GERP RS		1.3
Varity_R		0.038
gMVP		0.095

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: chr3-193130086;