Variant 10-3138035-T-C 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.3110A>G(p.Gln1037Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 1,593,702 control chromosomes in the GnomAD database, including 404,664 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 same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.70 ( 37522 hom., cov: 33)

Exomes 𝑓: 0.71 ( 367142 hom. )

Consequence

PITRM1
NM_014889.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.939

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:

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=1.0319361E-6).

BP6

Variant 10-3138035-T-C is Benign according to our data. Variant chr10-3138035-T-C is described in ClinVar as [Benign]. Clinvar id is 1598743.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PITRM1	NM_014889.4 linkuse as main transcript	c.3110A>G	p.Gln1037Arg	missense_variant	27/27	ENST00000224949.9	NP_055704.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PITRM1	ENST00000224949.9 linkuse as main transcript	c.3110A>G	p.Gln1037Arg	missense_variant	27/27	1	NM_014889.4	ENSP00000224949	P3	Q5JRX3-1

Frequencies

GnomAD3 genomes

AF:

0.702

AC:

106666

AN:

151958

Hom.:

37495

Cov.:

show subpopulations

Gnomad AFR

AF:

0.710

Gnomad AMI

AF:

0.668

Gnomad AMR

AF:

0.679

Gnomad ASJ

AF:

0.611

Gnomad EAS

AF:

0.740

Gnomad SAS

AF:

0.714

Gnomad FIN

AF:

0.696

Gnomad MID

AF:

0.601

Gnomad NFE

AF:

0.705

Gnomad OTH

AF:

0.712

GnomAD3 exomes

AF:

0.702

AC:

163342

AN:

232586

Hom.:

57408

AF XY:

0.702

AC XY:

88250

AN XY:

125792

show subpopulations

Gnomad AFR exome

AF:

0.707

Gnomad AMR exome

AF:

0.713

Gnomad ASJ exome

AF:

0.612

Gnomad EAS exome

AF:

0.738

Gnomad SAS exome

AF:

0.716

Gnomad FIN exome

AF:

0.688

Gnomad NFE exome

AF:

0.701

Gnomad OTH exome

AF:

0.687

GnomAD4 exome

AF:

0.713

AC:

1027768

AN:

1441626

Hom.:

367142

Cov.:

AF XY:

0.712

AC XY:

510074

AN XY:

716474

show subpopulations

Gnomad4 AFR exome

AF:

0.713

Gnomad4 AMR exome

AF:

0.707

Gnomad4 ASJ exome

AF:

0.613

Gnomad4 EAS exome

AF:

0.751

Gnomad4 SAS exome

AF:

0.712

Gnomad4 FIN exome

AF:

0.688

Gnomad4 NFE exome

AF:

0.716

Gnomad4 OTH exome

AF:

0.701

GnomAD4 genome

AF:

0.702

AC:

106738

AN:

152076

Hom.:

37522

Cov.:

AF XY:

0.702

AC XY:

52191

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.709

Gnomad4 AMR

AF:

0.680

Gnomad4 ASJ

AF:

0.611

Gnomad4 EAS

AF:

0.740

Gnomad4 SAS

AF:

0.714

Gnomad4 FIN

AF:

0.696

Gnomad4 NFE

AF:

0.705

Gnomad4 OTH

AF:

0.707

Alfa

AF:

0.699

Hom.:

76750

Bravo

AF:

0.703

TwinsUK

AF:

0.717

AC:

2658

ALSPAC

AF:

0.726

AC:

2799

ESP6500AA

AF:

0.723

AC:

2947

ESP6500EA

AF:

0.710

AC:

5936

ExAC

AF:

0.688

AC:

82842

Asia WGS

AF:

0.690

AC:

2399

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.73

CADD

Benign

2.8

DANN

Benign

0.39

DEOGEN2

Benign

0.019

T;.;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.087

LIST_S2

Benign

0.38

T;T;T;T

MetaRNN

Benign

0.0000010

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-2.9

N;.;.;.

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.32

PROVEAN

Benign

0.64

N;N;N;N

REVEL

Benign

0.11

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Vest4

0.028

MPC

0.054

ClinPred

0.0064

GERP RS

0.73

Varity_R

0.033

gMVP

0.41

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