NM_032279.4:c.3314T>A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2504925).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032279.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP13A4	NM_032279.4	MANE Select	c.3314T>A	p.Val1105Asp	missense	Exon 29 of 30	NP_115655.2	Q4VNC1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP13A4	ENST00000342695.9	TSL:1 MANE Select	c.3314T>A	p.Val1105Asp	missense	Exon 29 of 30	ENSP00000339182.4	Q4VNC1-1
	ATP13A4	ENST00000400270.6	TSL:1	c.362T>A	p.Val121Asp	missense	Exon 6 of 7	ENSP00000383129.2	Q4VNC1-4
	ATP13A4	ENST00000392443.7	TSL:5	c.3257T>A	p.Val1086Asp	missense	Exon 29 of 30	ENSP00000376238.3	B7WPN9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.81	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.27
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.026	D
Sift4G	Uncertain	0.011	D
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
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

hg19: chr3-193125166;