Variant 10-3145630-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_014889.4(PITRM1):c.2423A>G(p.Lys808Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000271 in 1,550,050 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 35)

Exomes 𝑓: 0.00028 ( 3 hom. )

Consequence

PITRM1
NM_014889.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.11

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:):

PITRM1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0047854483).

BP6

Variant 10-3145630-T-C is Benign according to our data. Variant chr10-3145630-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1552281.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PITRM1	NM_014889.4 linkuse as main transcript	c.2423A>G	p.Lys808Arg	missense_variant	21/27	ENST00000224949.9	NP_055704.2	Q5JRX3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PITRM1	ENST00000224949.9 linkuse as main transcript	c.2423A>G	p.Lys808Arg	missense_variant	21/27	1	NM_014889.4	ENSP00000224949.4		Q5JRX3-1

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152268

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00434

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000665

AC:

105

AN:

157976

Hom.:

AF XY:

0.000792

AC XY:

AN XY:

83338

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000121

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00417

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000325

Gnomad OTH exome

AF:

0.00112

GnomAD4 exome

AF:

0.000277

AC:

387

AN:

1397664

Hom.:

Cov.:

AF XY:

0.000384

AC XY:

265

AN XY:

689336

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000140

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00395

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000315

Gnomad4 OTH exome

AF:

0.000501

GnomAD4 genome

AF:

0.000217

AC:

AN:

152386

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74528

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00435

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.0000893

Hom.:

Bravo

AF:

0.0000869

ExAC

AF:

0.000504

AC:

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 02, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.45

CADD

Benign

9.5

DANN

Uncertain

0.99

DEOGEN2

Benign

0.019

T;.;.;T;T

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.49

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.74

T;T;T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.0048

T;T;T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.2

M;.;.;.;.

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.1

N;N;N;N;D

REVEL

Benign

0.13

Sift

Uncertain

0.025

D;D;T;D;D

Sift4G

Uncertain

0.037

D;D;D;D;.

Polyphen

0.45

B;.;.;.;.

Vest4

0.13

MutPred

0.36

Loss of methylation at K808 (P = 0.0151);.;.;.;.;

MVP

0.58

MPC

0.048

ClinPred

0.050

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.35

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