1-161304965-T-TTCTC
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_000530.8(MPZ):c.*910_*911insGAGA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 149,882 control chromosomes in the GnomAD database, including 1,305 homozygotes. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.13 ( 1302 hom., cov: 26)
Exomes 𝑓: 0.12 ( 3 hom. )
Consequence
MPZ
NM_000530.8 3_prime_UTR
NM_000530.8 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.360
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 Benign. Variant got -16 ACMG points.
BP6
Variant 1-161304965-T-TTCTC is Benign according to our data. Variant chr1-161304965-T-TTCTC is described in ClinVar as [Benign]. Clinvar id is 293302.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MPZ | NM_000530.8 | c.*910_*911insGAGA | 3_prime_UTR_variant | 6/6 | ENST00000533357.5 | NP_000521.2 | ||
MPZ | NM_001315491.2 | c.*718_*719insGAGA | 3_prime_UTR_variant | 6/6 | NP_001302420.1 | |||
MPZ | XM_017001321.3 | c.676-625_676-624insGAGA | intron_variant | XP_016856810.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MPZ | ENST00000533357.5 | c.*910_*911insGAGA | 3_prime_UTR_variant | 6/6 | 1 | NM_000530.8 | ENSP00000432943 | P1 |
Frequencies
GnomAD3 genomes AF: 0.130 AC: 19335AN: 149126Hom.: 1292 Cov.: 26
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GnomAD4 exome AF: 0.123 AC: 78AN: 636Hom.: 3 Cov.: 0 AF XY: 0.139 AC XY: 53AN XY: 380
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GnomAD4 genome AF: 0.130 AC: 19369AN: 149246Hom.: 1302 Cov.: 26 AF XY: 0.129 AC XY: 9372AN XY: 72720
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Charcot-Marie-Tooth disease type 4E Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Roussy-Lévy syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 13, 2021 | - - |
Charcot-Marie-Tooth disease, type I Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Charcot-Marie-Tooth, Intermediate Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at