Variant 10-3138124-T-C 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.3021A>G(p.Arg1007Arg) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 1,598,882 control chromosomes in the GnomAD database, including 281,935 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 29132 hom., cov: 32)

Exomes 𝑓: 0.59 ( 252803 hom. )

Consequence

PITRM1
NM_014889.4 splice_region, synonymous

Scores

Splicing: ADA: 0.00003535

Clinical Significance

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

Conservation

PhyloP100: 0.360

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 (HGNC:):

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=-0.69).

BP6

Variant 10-3138124-T-C is Benign according to our data. Variant chr10-3138124-T-C is described in ClinVar as [Benign]. Clinvar id is 1600344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.36 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.677 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.3021A>G	p.Arg1007Arg	splice_region_variant, synonymous_variant	27/27	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.3021A>G	p.Arg1007Arg	splice_region_variant, synonymous_variant	27/27	1	NM_014889.4	ENSP00000224949.4		Q5JRX3-1

Frequencies

GnomAD3 genomes

AF:

0.617

AC:

93831

AN:

151960

Hom.:

29106

Cov.:

show subpopulations

Gnomad AFR

AF:

0.683

Gnomad AMI

AF:

0.584

Gnomad AMR

AF:

0.580

Gnomad ASJ

AF:

0.554

Gnomad EAS

AF:

0.515

Gnomad SAS

AF:

0.537

Gnomad FIN

AF:

0.672

Gnomad MID

AF:

0.573

Gnomad NFE

AF:

0.595

Gnomad OTH

AF:

0.612

GnomAD3 exomes

AF:

0.592

AC:

141822

AN:

239608

Hom.:

42124

AF XY:

0.590

AC XY:

76572

AN XY:

129864

show subpopulations

Gnomad AFR exome

AF:

0.684

Gnomad AMR exome

AF:

0.573

Gnomad ASJ exome

AF:

0.561

Gnomad EAS exome

AF:

0.515

Gnomad SAS exome

AF:

0.538

Gnomad FIN exome

AF:

0.678

Gnomad NFE exome

AF:

0.598

Gnomad OTH exome

AF:

0.603

GnomAD4 exome

AF:

0.589

AC:

852281

AN:

1446804

Hom.:

252803

Cov.:

AF XY:

0.587

AC XY:

422561

AN XY:

719676

show subpopulations

Gnomad4 AFR exome

AF:

0.691

Gnomad4 AMR exome

AF:

0.578

Gnomad4 ASJ exome

AF:

0.554

Gnomad4 EAS exome

AF:

0.527

Gnomad4 SAS exome

AF:

0.537

Gnomad4 FIN exome

AF:

0.671

Gnomad4 NFE exome

AF:

0.590

Gnomad4 OTH exome

AF:

0.586

GnomAD4 genome

AF:

0.617

AC:

93903

AN:

152078

Hom.:

29132

Cov.:

AF XY:

0.616

AC XY:

45773

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.683

Gnomad4 AMR

AF:

0.580

Gnomad4 ASJ

AF:

0.554

Gnomad4 EAS

AF:

0.514

Gnomad4 SAS

AF:

0.536

Gnomad4 FIN

AF:

0.672

Gnomad4 NFE

AF:

0.595

Gnomad4 OTH

AF:

0.610

Alfa

AF:

0.593

Hom.:

45268

Bravo

AF:

0.614

Asia WGS

AF:

0.521

AC:

1813

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

BayesDel_noAF

Benign

-0.69

CADD

Benign

6.5

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000035

dbscSNV1_RF

Benign

0.0020

SpliceAI score (max)

0.010

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