2-24793223-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_ModeratePP5_Moderate

The NM_001013663.2(PTRHD1):c.155G>A(p.Cys52Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PTRHD1
NM_001013663.2 missense

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 6.94

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.932

PP5

Variant 2-24793223-C-T is Pathogenic according to our data. Variant chr2-24793223-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 375734.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTRHD1	NM_001013663.2 linkuse as main transcript	c.155G>A	p.Cys52Tyr	missense_variant	1/2	ENST00000328379.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTRHD1	ENST00000328379.6 linkuse as main transcript	c.155G>A	p.Cys52Tyr	missense_variant	1/2	1	NM_001013663.2	P1
CENPO	ENST00000473706.5 linkuse as main transcript	c.-251C>T		5_prime_UTR_variant	1/7	2			Q9BU64-2
CENPO	ENST00000473476.5 linkuse as main transcript	n.29+59C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

250246

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135638

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461074

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726884

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: 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

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 13, 2024

- -

Parkinsonian disorder

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München

Dec 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.13

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Pathogenic

0.84

Eigen

Pathogenic

0.98

Eigen_PC

Pathogenic

0.94

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.97

M_CAP

Uncertain

0.092

MetaRNN

Pathogenic

0.93

MetaSVM

Benign

-0.79

MutationAssessor

Pathogenic

3.2

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-11

REVEL

Uncertain

0.47

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.90

MutPred

0.75

Gain of disorder (P = 0.1103);

MVP

0.38

MPC

1.0

ClinPred

1.0

GERP RS

6.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.95

gMVP

0.81

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

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