chr3-193402704-C-T

Variant names:

• chr3-193402704-C-T
• NM_032279.4:c.3539G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032279.4(ATP13A4):​c.3539G>A​(p.Arg1180Lys) 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. 17/22 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: 0.228
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.027971208).

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.3539G>A	p.Arg1180Lys	missense	Exon 30 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.3539G>A	p.Arg1180Lys	missense	Exon 30 of 30	ENSP00000339182.4	Q4VNC1-1
	ATP13A4	ENST00000400270.6	TSL:1	c.587G>A	p.Arg196Lys	missense	Exon 7 of 7	ENSP00000383129.2	Q4VNC1-4
	ATP13A4	ENST00000392443.7	TSL:5	c.3482G>A	p.Arg1161Lys	missense	Exon 30 of 30	ENSP00000376238.3	B7WPN9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 18

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	0.066
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	0.29
DANN	Benign	0.33
DEOGEN2	Benign	0.0025	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0091	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.23
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.54	N
REVEL	Benign	0.084
Sift	Benign	1.0	T
Sift4G	Benign	0.80	T
Polyphen		0.0	B
Vest4		0.10
MutPred		0.20		Gain of ubiquitination at R1180 (P = 0.001)
MVP		0.26
MPC		0.12
ClinPred		0.028	T
GERP RS		-0.019
Varity_R		0.039
gMVP		0.46
Mutation Taster		=84/16	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: chr3-193120493;