Variant chr10-3138106-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014889.4(PITRM1):c.3039G>A(p.Lys1013=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,604,876 control chromosomes in the GnomAD database, including 59,929 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5697 hom., cov: 33)

Exomes 𝑓: 0.27 ( 54232 hom. )

Consequence

PITRM1
NM_014889.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.24

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 10-3138106-C-T is Benign according to our data. Variant chr10-3138106-C-T is described in ClinVar as [Benign]. Clinvar id is 1600998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.24 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PITRM1	NM_014889.4 linkuse as main transcript	c.3039G>A	p.Lys1013=	synonymous_variant	27/27	ENST00000224949.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PITRM1	ENST00000224949.9 linkuse as main transcript	c.3039G>A	p.Lys1013=	synonymous_variant	27/27	1	NM_014889.4	P3	Q5JRX3-1

Frequencies

GnomAD3 genomes

AF:

0.271

AC:

41203

AN:

151996

Hom.:

5696

Cov.:

show subpopulations

Gnomad AFR

AF:

0.234

Gnomad AMI

AF:

0.368

Gnomad AMR

AF:

0.314

Gnomad ASJ

AF:

0.364

Gnomad EAS

AF:

0.172

Gnomad SAS

AF:

0.205

Gnomad FIN

AF:

0.316

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.283

Gnomad OTH

AF:

0.288

GnomAD3 exomes

AF:

0.274

AC:

65964

AN:

240588

Hom.:

9201

AF XY:

0.272

AC XY:

35419

AN XY:

130400

show subpopulations

Gnomad AFR exome

AF:

0.236

Gnomad AMR exome

AF:

0.304

Gnomad ASJ exome

AF:

0.371

Gnomad EAS exome

AF:

0.169

Gnomad SAS exome

AF:

0.208

Gnomad FIN exome

AF:

0.321

Gnomad NFE exome

AF:

0.286

Gnomad OTH exome

AF:

0.292

GnomAD4 exome

AF:

0.271

AC:

393251

AN:

1452764

Hom.:

54232

Cov.:

AF XY:

0.269

AC XY:

194624

AN XY:

722372

show subpopulations

Gnomad4 AFR exome

AF:

0.237

Gnomad4 AMR exome

AF:

0.308

Gnomad4 ASJ exome

AF:

0.366

Gnomad4 EAS exome

AF:

0.169

Gnomad4 SAS exome

AF:

0.211

Gnomad4 FIN exome

AF:

0.320

Gnomad4 NFE exome

AF:

0.273

Gnomad4 OTH exome

AF:

0.282

GnomAD4 genome

AF:

0.271

AC:

41227

AN:

152112

Hom.:

5697

Cov.:

AF XY:

0.271

AC XY:

20179

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.234

Gnomad4 AMR

AF:

0.315

Gnomad4 ASJ

AF:

0.364

Gnomad4 EAS

AF:

0.172

Gnomad4 SAS

AF:

0.204

Gnomad4 FIN

AF:

0.316

Gnomad4 NFE

AF:

0.283

Gnomad4 OTH

AF:

0.287

Alfa

AF:

0.284

Hom.:

8149

Bravo

AF:

0.272

Asia WGS

AF:

0.186

AC:

647

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

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	- -

PITRM1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 30, 2019

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

BayesDel_noAF

Benign

-0.56

CADD

Benign

1.4

DANN

Benign

0.76

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