chr17-15230946-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM1BP4_Moderate
The NM_000304.4(PMP22):āc.454A>Gā(p.Ile152Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,614,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_000304.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PMP22 | NM_000304.4 | c.454A>G | p.Ile152Val | missense_variant | 5/5 | ENST00000312280.9 | NP_000295.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152200Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251270Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135804
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461822Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 727218
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152200Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74340
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease, type I Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Apr 25, 2024 | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 152 of the PMP22 protein (p.Ile152Val). This variant is present in population databases (no rsID available, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with PMP22-related conditions. ClinVar contains an entry for this variant (Variation ID: 531700). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PMP22 protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at