10-3144334-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_014889.4(PITRM1):ā€‹c.2490C>Gā€‹(p.Ala830Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00812 in 1,562,510 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.0055 ( 5 hom., cov: 33)
Exomes š‘“: 0.0084 ( 85 hom. )

Consequence

PITRM1
NM_014889.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.66
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-AS1 (HGNC:44675): (PITRM1 antisense RNA 1)

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 (BayesDel_noAF=-0.92).
BP6
Variant 10-3144334-G-C is Benign according to our data. Variant chr10-3144334-G-C is described in ClinVar as [Benign]. Clinvar id is 1666348.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0084 (11847/1410348) while in subpopulation MID AF= 0.0241 (138/5722). AF 95% confidence interval is 0.0208. There are 85 homozygotes in gnomad4_exome. There are 6015 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PITRM1NM_014889.4 linkc.2490C>G p.Ala830Ala synonymous_variant 22/27 ENST00000224949.9 NP_055704.2 Q5JRX3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PITRM1ENST00000224949.9 linkc.2490C>G p.Ala830Ala synonymous_variant 22/271 NM_014889.4 ENSP00000224949.4 Q5JRX3-1

Frequencies

GnomAD3 genomes
AF:
0.00555
AC:
844
AN:
152044
Hom.:
5
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00128
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00373
Gnomad ASJ
AF:
0.0153
Gnomad EAS
AF:
0.0108
Gnomad SAS
AF:
0.0127
Gnomad FIN
AF:
0.00113
Gnomad MID
AF:
0.0348
Gnomad NFE
AF:
0.00772
Gnomad OTH
AF:
0.00765
GnomAD3 exomes
AF:
0.00777
AC:
1352
AN:
174066
Hom.:
10
AF XY:
0.00885
AC XY:
820
AN XY:
92604
show subpopulations
Gnomad AFR exome
AF:
0.00106
Gnomad AMR exome
AF:
0.00404
Gnomad ASJ exome
AF:
0.0194
Gnomad EAS exome
AF:
0.00969
Gnomad SAS exome
AF:
0.0140
Gnomad FIN exome
AF:
0.000969
Gnomad NFE exome
AF:
0.00767
Gnomad OTH exome
AF:
0.0114
GnomAD4 exome
AF:
0.00840
AC:
11847
AN:
1410348
Hom.:
85
Cov.:
29
AF XY:
0.00863
AC XY:
6015
AN XY:
696768
show subpopulations
Gnomad4 AFR exome
AF:
0.00159
Gnomad4 AMR exome
AF:
0.00379
Gnomad4 ASJ exome
AF:
0.0187
Gnomad4 EAS exome
AF:
0.0107
Gnomad4 SAS exome
AF:
0.0144
Gnomad4 FIN exome
AF:
0.00116
Gnomad4 NFE exome
AF:
0.00820
Gnomad4 OTH exome
AF:
0.00932
GnomAD4 genome
AF:
0.00553
AC:
842
AN:
152162
Hom.:
5
Cov.:
33
AF XY:
0.00512
AC XY:
381
AN XY:
74400
show subpopulations
Gnomad4 AFR
AF:
0.00130
Gnomad4 AMR
AF:
0.00373
Gnomad4 ASJ
AF:
0.0153
Gnomad4 EAS
AF:
0.0106
Gnomad4 SAS
AF:
0.0127
Gnomad4 FIN
AF:
0.00113
Gnomad4 NFE
AF:
0.00772
Gnomad4 OTH
AF:
0.00710
Alfa
AF:
0.00891
Hom.:
1
Bravo
AF:
0.00535
Asia WGS
AF:
0.0140
AC:
49
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenOct 01, 2024PITRM1: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 12, 2024- -
PITRM1-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesNov 25, 2019This 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
-0.92
CADD
Benign
0.091
DANN
Benign
0.48
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
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.

Other links and lift over

dbSNP: rs59654932; hg19: chr10-3186526; COSMIC: COSV56540268; API