rs863225028
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM5BP4_StrongBP6_Very_Strong
The ENST00000395938.7(PMP22):c.316C>T(p.Arg106Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 4/5 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R106S) has been classified as Pathogenic.
Frequency
Consequence
ENST00000395938.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PMP22 | NM_000304.4 | c.327C>T | p.Cys109= | synonymous_variant | 5/5 | ENST00000312280.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PMP22 | ENST00000312280.9 | c.327C>T | p.Cys109= | synonymous_variant | 5/5 | 1 | NM_000304.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000659 AC: 1AN: 151806Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000799 AC: 2AN: 250234Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135518
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461342Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5AN XY: 726962
GnomAD4 genome ? AF: 0.00000659 AC: 1AN: 151806Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74164
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:1
Uncertain significance, no assertion criteria provided | literature only | Inherited Neuropathy Consortium | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 19, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 11, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Charcot-Marie-Tooth disease, type I Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Mar 11, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at