3-194406081-GG-AC

Variant names:

• chr3-194406081-GG-AC
• NM_001367549.1:c.3608_3609delCCinsGT
• ATP13A3 p.Pro1203Arg

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001367549.1(ATP13A3):​c.3608_3609delCCinsGT​(p.Pro1203Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATP13A3 NM_001367549.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.72
• 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.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.3608_3609delCCinsGT	p.Pro1203Arg	missense	N/A	NP_001354478.1	A0A2R8Y635
	ATP13A3	NM_001374836.1		c.3527_3528delCCinsGT	p.Pro1176Arg	missense	N/A	NP_001361765.1
	ATP13A3	NM_001437993.1		c.3518_3519delCCinsGT	p.Pro1173Arg	missense	N/A	NP_001424922.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP13A3	ENST00000645319.2	MANE Select	c.3608_3609delCCinsGT	p.Pro1203Arg	missense	N/A	ENSP00000494937.2	A0A2R8Y635
	ATP13A3	ENST00000429136.7	TSL:1	n.1454_1455delCCinsGT		non_coding_transcript_exon	Exon 13 of 13
	ATP13A3	ENST00000461660.2	TSL:1	n.712_713delCCinsGT		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-194126810;