3-194406005-C-T

Variant names:

• chr3-194406005-C-T
• rs200914446
• NM_001367549.1:c.3685G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001367549.1(ATP13A3):​c.3685G>A​(p.Glu1229Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATP13A3 NM_001367549.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.88
• Publications: 0 publications found

Genes affected

ATP13A3 (HGNC:24113): (ATPase 13A3) ATP13A3 is a member of the P-type ATPase family of proteins that transport a variety of cations across membranes. Other P-type ATPases include ATP7B (MIM 606882) and ATP7A (MIM 300011).[supplied by OMIM, Aug 2008]

ATP13A3 Gene-Disease associations (from GenCC):

• pulmonary arterial hypertension

  Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38937432).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367549.1. 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
	ATP13A3	NM_001367549.1	MANE Select	c.3685G>A	p.Glu1229Lys	missense	Exon 34 of 34	NP_001354478.1	A0A2R8Y635
	ATP13A3	NM_001374836.1		c.3604G>A	p.Glu1202Lys	missense	Exon 33 of 33	NP_001361765.1
	ATP13A3	NM_001437993.1		c.3595G>A	p.Glu1199Lys	missense	Exon 33 of 33	NP_001424922.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP13A3	ENST00000645319.2	MANE Select	c.3685G>A	p.Glu1229Lys	missense	Exon 34 of 34	ENSP00000494937.2	A0A2R8Y635
	ATP13A3	ENST00000429136.7	TSL:1	n.1531G>A		non_coding_transcript_exon	Exon 13 of 13
	ATP13A3	ENST00000461660.2	TSL:1	n.789G>A		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.031	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		6.9
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.080
Sift	Benign	0.33	T
Sift4G	Benign	0.49	T
Polyphen		0.016	B
Vest4		0.29
MutPred		0.43		Gain of methylation at E1199 (P = 0.0024)
MVP		0.16
MPC		0.53
ClinPred		0.96	D
GERP RS		5.6
Varity_R		0.27
gMVP		0.45
Mutation Taster		=87/13	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

dbSNP: rs200914446; hg19: chr3-194126734;