rs201192820
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_000304.4(PMP22):c.87C>T(p.Ile29=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000161 in 1,611,304 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00014 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00016 ( 0 hom. )
Consequence
PMP22
NM_000304.4 synonymous
NM_000304.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.143
Genes affected
PMP22 (HGNC:9118): (peripheral myelin protein 22) This gene encodes an integral membrane protein that is a major component of myelin in the peripheral nervous system. Studies suggest two alternately used promoters drive tissue-specific expression. Various mutations of this gene are causes of Charcot-Marie-Tooth disease Type IA, Dejerine-Sottas syndrome, and hereditary neuropathy with liability to pressure palsies. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
?
Variant 17-15259185-G-A is Benign according to our data. Variant chr17-15259185-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 462782.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-15259185-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.143 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PMP22 | NM_000304.4 | c.87C>T | p.Ile29= | synonymous_variant | 3/5 | ENST00000312280.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PMP22 | ENST00000312280.9 | c.87C>T | p.Ile29= | synonymous_variant | 3/5 | 1 | NM_000304.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000145 AC: 22AN: 152134Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000676 AC: 17AN: 251406Hom.: 0 AF XY: 0.0000810 AC XY: 11AN XY: 135872
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GnomAD4 exome AF: 0.000163 AC: 238AN: 1459052Hom.: 0 Cov.: 30 AF XY: 0.000169 AC XY: 123AN XY: 726044
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GnomAD4 genome ? AF: 0.000144 AC: 22AN: 152252Hom.: 0 Cov.: 31 AF XY: 0.000134 AC XY: 10AN XY: 74460
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ClinVar
Significance: Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 23, 2020 | This variant is associated with the following publications: (PMID: 9888385) - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2019 | - - |
Charcot-Marie-Tooth disease Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Molecular Genetics Laboratory, London Health Sciences Centre | - | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 13, 2023 | 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. - |
PMP22-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 30, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Charcot-Marie-Tooth disease, type I Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 17, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
Benign
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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