10-3138035-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014889.4(PITRM1):​c.3110A>T​(p.Gln1037Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q1037R) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

PITRM1
NM_014889.4 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09636733).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PITRM1NM_014889.4 linkuse as main transcriptc.3110A>T p.Gln1037Leu missense_variant 27/27 ENST00000224949.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PITRM1ENST00000224949.9 linkuse as main transcriptc.3110A>T p.Gln1037Leu missense_variant 27/271 NM_014889.4 P3Q5JRX3-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
6.92e-7
AC:
1
AN:
1444304
Hom.:
0
Cov.:
29
AF XY:
0.00000139
AC XY:
1
AN XY:
717774
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.08e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
14
DANN
Benign
0.93
DEOGEN2
Benign
0.024
T;.;.;T
Eigen
Benign
-0.85
Eigen_PC
Benign
-0.85
FATHMM_MKL
Benign
0.68
D
LIST_S2
Benign
0.66
T;T;T;T
M_CAP
Benign
0.044
D
MetaRNN
Benign
0.096
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.55
N;.;.;.
MutationTaster
Benign
1.0
P;P;P;P
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-0.13
N;N;N;N
REVEL
Benign
0.12
Sift
Uncertain
0.0090
D;D;D;D
Sift4G
Uncertain
0.017
D;D;D;D
Vest4
0.14
MutPred
0.43
.;Gain of stability (P = 0.0061);.;.;
MVP
0.12
MPC
0.050
ClinPred
0.69
D
GERP RS
0.73
Varity_R
0.11
gMVP
0.60

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.

Other links and lift over

dbSNP: rs6901; hg19: chr10-3180227; API