Variant 2-24793181-GGGTGGTCGCGGTGAGTGTGCAAGGCCGC-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate

The NM_001013663.2(PTRHD1):c.169_196delGCGGCCTTGCACACTCACCGCGACCACC(p.Ala57ArgfsTer26) variant causes a frameshift change. The variant allele was found at a frequency of 0.000162 in 1,613,408 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

PTRHD1
NM_001013663.2 frameshift

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 7.04

Variant links:

Genes affected

PTRHD1 (HGNC:33782): (peptidyl-tRNA hydrolase domain containing 1) This gene encodes the enzyme peptidyl-tRNA hydrolase. Peptidyl-tRNA hydrolases perform the essential function of recycling peptidyl-tRNAs. Mutations in this gene are associated with autosomal-recessive intellectual disability and parkinsonism. [provided by RefSeq, May 2017]

PTRHD1 links:

CENPO (HGNC:28152): (centromere protein O) This gene encodes a component of the interphase centromere complex. The encoded protein is localized to the centromere throughout the cell cycle and is required for bipolar spindle assembly, chromosome segregation and checkpoint signaling during mitosis. Alternatively spliced transcript variants encoding multiple protein isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

CENPO links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 2-24793181-GGGTGGTCGCGGTGAGTGTGCAAGGCCGC-G is Pathogenic according to our data. Variant chr2-24793181-GGGTGGTCGCGGTGAGTGTGCAAGGCCGC-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3061964.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTRHD1	NM_001013663.2 link	c.169_196delGCGGCCTTGCACACTCACCGCGACCACC	p.Ala57ArgfsTer26	frameshift_variant	Exon 1 of 2	ENST00000328379.6	NP_001013685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PTRHD1	ENST00000328379.6 link	c.169_196delGCGGCCTTGCACACTCACCGCGACCACC	p.Ala57ArgfsTer26	frameshift_variant	Exon 1 of 2	1	NM_001013663.2	ENSP00000330389.4	Q6GMV3
CENPO	ENST00000473706 link	c.-287_-260delTCGCGGTGAGTGTGCAAGGCCGCGGTGG		5_prime_UTR_variant	Exon 1 of 7	2		ENSP00000417787.1	Q9BU64-2
CENPO	ENST00000473476.5 link	n.29+23_29+50delTCGCGGTGAGTGTGCAAGGCCGCGGTGG		intron_variant	Intron 1 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.000486

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000136

AC:

AN:

250020

Hom.:

AF XY:

0.0000812

AC XY:

AN XY:

135492

show subpopulations

Gnomad AFR exome

AF:

0.00149

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000621

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000128

AC:

187

AN:

1461082

Hom.:

AF XY:

0.000117

AC XY:

AN XY:

726882

show subpopulations

Gnomad4 AFR exome

AF:

0.00206

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000989

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.000492

AC:

AN:

152326

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00159

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000349

Hom.:

Bravo

AF:

0.000518

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities

Pathogenic:1

Mar 13, 2024

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

not provided

Pathogenic:1

Jul 15, 2024

GeneDx

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Frameshift variant predicted to result in abnormal protein length as the last 84 amino acids are replaced with 25 different amino acids; This variant is associated with the following publications: (PMID: 36344539, 30398675, 34765690) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over