rs3814596

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_014889.4(PITRM1):c.506T>C(p.Phe169Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,610,222 control chromosomes in the GnomAD database, including 28,845 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 0.17 ( 2217 hom., cov: 32)

Exomes 𝑓: 0.19 ( 26628 hom. )

Consequence

PITRM1
NM_014889.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 8.66

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=0.0032638013).

BP6

Variant 10-3165440-A-G is Benign according to our data. Variant chr10-3165440-A-G is described in ClinVar as [Benign]. Clinvar id is 1600892.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PITRM1	NM_014889.4 link	c.506T>C	p.Phe169Ser	missense_variant	Exon 5 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.506T>C	p.Phe169Ser	missense_variant	Exon 5 of 27	1	NM_014889.4	ENSP00000224949.4		Q5JRX3-1

Frequencies

GnomAD3 genomes

AF:

0.168

AC:

25534

AN:

152078

Hom.:

2216

Cov.:

show subpopulations

Gnomad AFR

AF:

0.143

Gnomad AMI

AF:

0.134

Gnomad AMR

AF:

0.118

Gnomad ASJ

AF:

0.209

Gnomad EAS

AF:

0.0506

Gnomad SAS

AF:

0.174

Gnomad FIN

AF:

0.224

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.192

Gnomad OTH

AF:

0.175

GnomAD3 exomes

AF:

0.166

AC:

41123

AN:

247752

Hom.:

3714

AF XY:

0.172

AC XY:

23132

AN XY:

134370

show subpopulations

Gnomad AFR exome

AF:

0.139

Gnomad AMR exome

AF:

0.0818

Gnomad ASJ exome

AF:

0.204

Gnomad EAS exome

AF:

0.0550

Gnomad SAS exome

AF:

0.182

Gnomad FIN exome

AF:

0.221

Gnomad NFE exome

AF:

0.194

Gnomad OTH exome

AF:

0.181

GnomAD4 exome

AF:

0.188

AC:

273490

AN:

1458026

Hom.:

26628

Cov.:

AF XY:

0.188

AC XY:

136520

AN XY:

725350

show subpopulations

Gnomad4 AFR exome

AF:

0.137

Gnomad4 AMR exome

AF:

0.0880

Gnomad4 ASJ exome

AF:

0.202

Gnomad4 EAS exome

AF:

0.0563

Gnomad4 SAS exome

AF:

0.183

Gnomad4 FIN exome

AF:

0.215

Gnomad4 NFE exome

AF:

0.197

Gnomad4 OTH exome

AF:

0.175

GnomAD4 genome

AF:

0.168

AC:

25535

AN:

152196

Hom.:

2217

Cov.:

AF XY:

0.166

AC XY:

12373

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.143

Gnomad4 AMR

AF:

0.118

Gnomad4 ASJ

AF:

0.209

Gnomad4 EAS

AF:

0.0503

Gnomad4 SAS

AF:

0.174

Gnomad4 FIN

AF:

0.224

Gnomad4 NFE

AF:

0.192

Gnomad4 OTH

AF:

0.174

Alfa

AF:

0.180

Hom.:

5425

Bravo

AF:

0.156

TwinsUK

AF:

0.200

AC:

741

ALSPAC

AF:

0.192

AC:

741

ESP6500AA

AF:

0.140

AC:

523

ESP6500EA

AF:

0.194

AC:

1599

ExAC

AF:

0.168

AC:

20283

Asia WGS

AF:

0.0990

AC:

347

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

- -

PITRM1-related disorder

Benign:1

Nov 26, 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

0.32

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.098

T;.;.

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.71

T;T;T

MetaRNN

Benign

0.0033

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

M;M;.

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.0

D;D;D

REVEL

Benign

0.17

Sift

Benign

0.20

T;T;T

Sift4G

Benign

0.43

T;T;T

Polyphen

0.75

P;P;.

Vest4

0.36

MPC

0.40

ClinPred

0.037

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.85

gMVP

0.79

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