rs2388556

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014889.4(PITRM1):c.1861G>A(p.Val621Ile) variant causes a missense change. The variant allele was found at a frequency of 0.165 in 1,566,790 control chromosomes in the GnomAD database, including 22,192 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.15 ( 1763 hom., cov: 32)

Exomes 𝑓: 0.17 ( 20429 hom. )

Consequence

PITRM1
NM_014889.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 5.86

Variant links:

Genes affected

PITRM1 (HGNC:17663): (pitrilysin metallopeptidase 1) The protein encoded by this gene is an ATP-dependent metalloprotease that degrades post-cleavage mitochondrial transit peptides. The encoded protein binds zinc and can also degrade amyloid beta A4 protein, suggesting a possible role in Alzheimer's disease. [provided by RefSeq, Dec 2016]

PITRM1 links:

PITRM1-AS1 (HGNC:44675): (PITRM1 antisense RNA 1)

PITRM1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022476315).

BP6

Variant 10-3149631-C-T is Benign according to our data. Variant chr10-3149631-C-T is described in ClinVar as [Benign]. Clinvar id is 1300268.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PITRM1	NM_014889.4 link	c.1861G>A	p.Val621Ile	missense_variant	Exon 16 of 27	ENST00000224949.9	NP_055704.2	Q5JRX3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PITRM1	ENST00000224949.9 link	c.1861G>A	p.Val621Ile	missense_variant	Exon 16 of 27	1	NM_014889.4	ENSP00000224949.4		Q5JRX3-1

Frequencies

GnomAD3 genomes

AF:

0.150

AC:

22716

AN:

151922

Hom.:

1762

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.0999

Gnomad ASJ

AF:

0.121

Gnomad EAS

AF:

0.0488

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.211

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.172

Gnomad OTH

AF:

0.146

GnomAD3 exomes

AF:

0.144

AC:

30838

AN:

213836

Hom.:

2496

AF XY:

0.148

AC XY:

17196

AN XY:

116250

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.0701

Gnomad ASJ exome

AF:

0.116

Gnomad EAS exome

AF:

0.0537

Gnomad SAS exome

AF:

0.144

Gnomad FIN exome

AF:

0.201

Gnomad NFE exome

AF:

0.170

Gnomad OTH exome

AF:

0.151

GnomAD4 exome

AF:

0.167

AC:

235926

AN:

1414750

Hom.:

20429

Cov.:

AF XY:

0.167

AC XY:

116664

AN XY:

700340

show subpopulations

Gnomad4 AFR exome

AF:

0.128

Gnomad4 AMR exome

AF:

0.0762

Gnomad4 ASJ exome

AF:

0.112

Gnomad4 EAS exome

AF:

0.0559

Gnomad4 SAS exome

AF:

0.144

Gnomad4 FIN exome

AF:

0.200

Gnomad4 NFE exome

AF:

0.177

Gnomad4 OTH exome

AF:

0.152

GnomAD4 genome

AF:

0.149

AC:

22714

AN:

152040

Hom.:

1763

Cov.:

AF XY:

0.149

AC XY:

11055

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.134

Gnomad4 AMR

AF:

0.0997

Gnomad4 ASJ

AF:

0.121

Gnomad4 EAS

AF:

0.0485

Gnomad4 SAS

AF:

0.129

Gnomad4 FIN

AF:

0.211

Gnomad4 NFE

AF:

0.172

Gnomad4 OTH

AF:

0.145

Alfa

AF:

0.159

Hom.:

4970

Bravo

AF:

0.138

TwinsUK

AF:

0.174

AC:

647

ALSPAC

AF:

0.164

AC:

632

ESP6500AA

AF:

0.130

AC:

532

ESP6500EA

AF:

0.172

AC:

1444

ExAC

AF:

0.143

AC:

17253

Asia WGS

AF:

0.0830

AC:

290

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 28, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PITRM1-related disorder

Benign:1

Nov 19, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

0.077

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

T;.;.;T

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.78

T;T;T;T

MetaRNN

Benign

0.0022

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;M;.;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.76

N;N;N;N

REVEL

Benign

0.085

Sift

Benign

0.18

T;T;T;T

Sift4G

Benign

0.17

T;T;T;D

Polyphen

0.97

D;.;.;.

Vest4

0.14

MPC

0.11

ClinPred

0.017

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.30

gMVP

0.42

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