Variant rs4242746 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_014889.4(PITRM1):c.982A>G(p.Ile328Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 1,597,334 control chromosomes in the GnomAD database, including 367,165 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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 0.65 ( 32026 hom., cov: 32)

Exomes 𝑓: 0.68 ( 335139 hom. )

Consequence

PITRM1
NM_014889.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.299

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=7.5671096E-6).

BP6

Variant 10-3159873-T-C is Benign according to our data. Variant chr10-3159873-T-C is described in ClinVar as [Benign]. Clinvar id is 1607453.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PITRM1	NM_014889.4 link	c.982A>G	p.Ile328Val	missense_variant	9/27	ENST00000224949.9	NP_055704.2	Q5JRX3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PITRM1	ENST00000224949.9 link	c.982A>G	p.Ile328Val	missense_variant	9/27	1	NM_014889.4	ENSP00000224949.4		Q5JRX3-1

Frequencies

GnomAD3 genomes

AF:

0.648

AC:

98393

AN:

151918

Hom.:

32011

Cov.:

show subpopulations

Gnomad AFR

AF:

0.629

Gnomad AMI

AF:

0.618

Gnomad AMR

AF:

0.570

Gnomad ASJ

AF:

0.564

Gnomad EAS

AF:

0.589

Gnomad SAS

AF:

0.666

Gnomad FIN

AF:

0.676

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.681

Gnomad OTH

AF:

0.647

GnomAD3 exomes

AF:

0.638

AC:

150572

AN:

235956

Hom.:

48388

AF XY:

0.643

AC XY:

81785

AN XY:

127242

show subpopulations

Gnomad AFR exome

AF:

0.627

Gnomad AMR exome

AF:

0.534

Gnomad ASJ exome

AF:

0.561

Gnomad EAS exome

AF:

0.580

Gnomad SAS exome

AF:

0.670

Gnomad FIN exome

AF:

0.678

Gnomad NFE exome

AF:

0.672

Gnomad OTH exome

AF:

0.638

GnomAD4 exome

AF:

0.679

AC:

981669

AN:

1445296

Hom.:

335139

Cov.:

AF XY:

0.678

AC XY:

487073

AN XY:

718210

show subpopulations

Gnomad4 AFR exome

AF:

0.634

Gnomad4 AMR exome

AF:

0.537

Gnomad4 ASJ exome

AF:

0.566

Gnomad4 EAS exome

AF:

0.592

Gnomad4 SAS exome

AF:

0.668

Gnomad4 FIN exome

AF:

0.679

Gnomad4 NFE exome

AF:

0.695

Gnomad4 OTH exome

AF:

0.655

GnomAD4 genome

AF:

0.648

AC:

98450

AN:

152038

Hom.:

32026

Cov.:

AF XY:

0.644

AC XY:

47882

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.628

Gnomad4 AMR

AF:

0.570

Gnomad4 ASJ

AF:

0.564

Gnomad4 EAS

AF:

0.589

Gnomad4 SAS

AF:

0.666

Gnomad4 FIN

AF:

0.676

Gnomad4 NFE

AF:

0.681

Gnomad4 OTH

AF:

0.643

Alfa

AF:

0.666

Hom.:

87223

Bravo

AF:

0.637

TwinsUK

AF:

0.698

AC:

2588

ALSPAC

AF:

0.711

AC:

2739

ESP6500AA

AF:

0.680

AC:

1373

ESP6500EA

AF:

0.691

AC:

2964

ExAC

AF:

0.630

AC:

75967

Asia WGS

AF:

0.599

AC:

2085

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.34

DANN

Benign

0.52

DEOGEN2

Benign

0.0069

T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.24

T;T;T

MetaRNN

Benign

0.0000076

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.57

N;N;.

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.11

N;N;N

REVEL

Benign

0.032

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.73

T;T;T

Vest4

0.057

MPC

0.045

ClinPred

0.0019

GERP RS

0.30

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.026

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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