chr10-3138096-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_014889.4(PITRM1):c.3049G>A(p.Gly1017Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0262 in 1,609,880 control chromosomes in the GnomAD database, including 672 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.019 ( 40 hom., cov: 34)
Exomes 𝑓: 0.027 ( 632 hom. )
Consequence
PITRM1
NM_014889.4 missense
NM_014889.4 missense
Scores
4
14
Clinical Significance
Conservation
PhyloP100: 3.84
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0100236535).
BP6
?
Variant 10-3138096-C-T is Benign according to our data. Variant chr10-3138096-C-T is described in ClinVar as [Benign]. Clinvar id is 1628450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0188 (2866/152290) while in subpopulation NFE AF= 0.0307 (2089/68030). AF 95% confidence interval is 0.0296. There are 40 homozygotes in gnomad4. There are 1258 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 40 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PITRM1 | NM_014889.4 | c.3049G>A | p.Gly1017Ser | missense_variant | 27/27 | ENST00000224949.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PITRM1 | ENST00000224949.9 | c.3049G>A | p.Gly1017Ser | missense_variant | 27/27 | 1 | NM_014889.4 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0188 AC: 2867AN: 152172Hom.: 40 Cov.: 34
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GnomAD3 exomes AF: 0.0180 AC: 4374AN: 242422Hom.: 70 AF XY: 0.0184 AC XY: 2417AN XY: 131342
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GnomAD4 exome AF: 0.0270 AC: 39326AN: 1457590Hom.: 632 Cov.: 34 AF XY: 0.0264 AC XY: 19128AN XY: 724570
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GnomAD4 genome ? AF: 0.0188 AC: 2866AN: 152290Hom.: 40 Cov.: 34 AF XY: 0.0169 AC XY: 1258AN XY: 74480
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131
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119
ESP6500AA
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2133
Asia WGS
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
PITRM1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 19, 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). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Uncertain
T;T;T;T
Polyphen
D;.;.;.
Vest4
MPC
0.061
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at