chr1-161305851-G-C
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_000530.8(MPZ):c.*25C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).
Frequency
Genomes: 𝑓 0.000041 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0077 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
MPZ
NM_000530.8 3_prime_UTR
NM_000530.8 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.68
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 -5 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
Variant 1-161305851-G-C is Benign according to our data. Variant chr1-161305851-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3355274.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MPZ | NM_000530.8 | c.*25C>G | 3_prime_UTR_variant | 6/6 | ENST00000533357.5 | NP_000521.2 | ||
MPZ | NM_001315491.2 | c.772C>G | p.Arg258Gly | missense_variant | 6/6 | NP_001302420.1 | ||
MPZ | XM_017001321.3 | c.675+257C>G | intron_variant | XP_016856810.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MPZ | ENST00000533357.5 | c.*25C>G | 3_prime_UTR_variant | 6/6 | 1 | NM_000530.8 | ENSP00000432943 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 6AN: 146222Hom.: 0 Cov.: 31 FAILED QC
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00770 AC: 4154AN: 539744Hom.: 0 Cov.: 16 AF XY: 0.00669 AC XY: 1944AN XY: 290406
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GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000410 AC: 6AN: 146352Hom.: 0 Cov.: 31 AF XY: 0.0000420 AC XY: 3AN XY: 71488
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
MPZ-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | May 24, 2024 | 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). - |
Computational scores
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Benign
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Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at