2-24793251-G-T

Position:

chr2-24793251-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001013663.2(PTRHD1):c.127C>A(p.Pro43Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0011 in 1,613,936 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.00055 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 44 hom. )

Consequence

PTRHD1
NM_001013663.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 6.91

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 Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009550095).

BP6

Variant 2-24793251-G-T is Benign according to our data. Variant chr2-24793251-G-T is described in ClinVar as [Benign]. Clinvar id is 3043675.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-24793251-G-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00116 (1689/1461548) while in subpopulation SAS AF= 0.0186 (1605/86258). AF 95% confidence interval is 0.0178. There are 44 homozygotes in gnomad4_exome. There are 1171 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTRHD1	NM_001013663.2 linkuse as main transcript	c.127C>A	p.Pro43Thr	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.127C>A	p.Pro43Thr	missense_variant	1/2	1	NM_001013663.2	P1
CENPO	ENST00000473706.5 linkuse as main transcript	c.-223G>T		5_prime_UTR_variant	1/7	2			Q9BU64-2
CENPO	ENST00000473476.5 linkuse as main transcript	n.30-55G>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.000558

AC:

AN:

152270

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0168

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00213

AC:

536

AN:

251056

Hom.:

AF XY:

0.00286

AC XY:

388

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0171

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.000980

GnomAD4 exome

AF:

0.00116

AC:

1689

AN:

1461548

Hom.:

Cov.:

AF XY:

0.00161

AC XY:

1171

AN XY:

727094

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000344

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0186

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.000894

GnomAD4 genome

AF:

0.000551

AC:

AN:

152388

Hom.:

Cov.:

AF XY:

0.000792

AC XY:

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.0000721

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0166

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000503

Hom.:

Bravo

AF:

0.000136

ExAC

AF:

0.00214

AC:

260

Asia WGS

AF:

0.00693

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PTRHD1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 14, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.63

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.90

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.73

MetaRNN

Benign

0.0096

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.60

PROVEAN

Pathogenic

-6.2

REVEL

Uncertain

0.32

Sift

Benign

0.033

Sift4G

Benign

0.061

Polyphen

1.0

Vest4

0.84

MutPred

0.57

Loss of loop (P = 0.0031);

MVP

0.43

MPC

0.57

ClinPred

0.12

GERP RS

6.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.55

gMVP

0.58

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