chr7-110663677-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_032549.4(IMMP2L):c.453G>T(p.Trp151Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000373 in 1,609,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
IMMP2L
NM_032549.4 missense
NM_032549.4 missense
Scores
9
7
2
Clinical Significance
Conservation
PhyloP100: 5.19
Genes affected
IMMP2L (HGNC:14598): (inner mitochondrial membrane peptidase subunit 2) This gene encodes a protein involved in processing the signal peptide sequences used to direct mitochondrial proteins to the mitochondria. The encoded protein resides in the mitochondria and is one of the necessary proteins for the catalytic activity of the mitochondrial inner membrane peptidase (IMP) complex. Two variants that encode the same protein have been described for this gene. [provided by RefSeq, Sep 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.846
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IMMP2L | NM_032549.4 | c.453G>T | p.Trp151Cys | missense_variant | 6/6 | ENST00000405709.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IMMP2L | ENST00000405709.7 | c.453G>T | p.Trp151Cys | missense_variant | 6/6 | 1 | NM_032549.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152102Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000206 AC: 3AN: 1457090Hom.: 0 Cov.: 28 AF XY: 0.00000276 AC XY: 2AN XY: 725018
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152220Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74424
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 08, 2024 | The c.453G>T (p.W151C) alteration is located in exon 6 (coding exon 5) of the IMMP2L gene. This alteration results from a G to T substitution at nucleotide position 453, causing the tryptophan (W) at amino acid position 151 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Uncertain
D;D;D;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;H;H;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D
Sift4G
Pathogenic
D;D;D;D
Polyphen
D;D;D;.
Vest4
MutPred
Loss of catalytic residue at W151 (P = 0.0823);Loss of catalytic residue at W151 (P = 0.0823);Loss of catalytic residue at W151 (P = 0.0823);.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -8
Find out detailed SpliceAI scores and Pangolin per-transcript scores at