1-161305875-G-A
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate
The NM_000530.8(MPZ):c.*1C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000345 in 1,451,278 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 0.000013 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000023 ( 0 hom. )
Consequence
MPZ
NM_000530.8 3_prime_UTR
NM_000530.8 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.22
Genes affected
MPZ (HGNC:7225): (myelin protein zero) This gene is specifically expressed in Schwann cells of the peripheral nervous system and encodes a type I transmembrane glycoprotein that is a major structural protein of the peripheral myelin sheath. The encoded protein contains a large hydrophobic extracellular domain and a smaller basic intracellular domain, which are essential for the formation and stabilization of the multilamellar structure of the compact myelin. Mutations in this gene are associated with autosomal dominant form of Charcot-Marie-Tooth disease type 1 (CMT1B) and other polyneuropathies, such as Dejerine-Sottas syndrome (DSS) and congenital hypomyelinating neuropathy (CHN). A recent study showed that two isoforms are produced from the same mRNA by use of alternative in-frame translation termination codons via a stop codon readthrough mechanism. [provided by RefSeq, Oct 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.31).
BP6
Variant 1-161305875-G-A is Benign according to our data. Variant chr1-161305875-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 917384.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MPZ | NM_000530.8 | c.*1C>T | 3_prime_UTR_variant | 6/6 | ENST00000533357.5 | ||
MPZ | NM_001315491.2 | c.748C>T | p.Arg250Trp | missense_variant | 6/6 | ||
MPZ | XM_017001321.3 | c.675+233C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MPZ | ENST00000533357.5 | c.*1C>T | 3_prime_UTR_variant | 6/6 | 1 | NM_000530.8 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000133 AC: 2AN: 150694Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249018Hom.: 0 AF XY: 0.00000742 AC XY: 1AN XY: 134736
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GnomAD4 exome AF: 0.00000231 AC: 3AN: 1300584Hom.: 0 Cov.: 30 AF XY: 0.00000154 AC XY: 1AN XY: 650708
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GnomAD4 genome AF: 0.0000133 AC: 2AN: 150694Hom.: 0 Cov.: 31 AF XY: 0.0000136 AC XY: 1AN XY: 73574
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Charcot-Marie-Tooth disease Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Molecular Genetics Laboratory, London Health Sciences Centre | - | - - |
Computational scores
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Benign
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Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at