chr1-161305851-G-C

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

Scores

2

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.68
Variant links:
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]

Genome browser will be placed here

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
MPZNM_000530.8 linkuse as main transcriptc.*25C>G 3_prime_UTR_variant 6/6 ENST00000533357.5 NP_000521.2
MPZNM_001315491.2 linkuse as main transcriptc.772C>G p.Arg258Gly missense_variant 6/6 NP_001302420.1
MPZXM_017001321.3 linkuse as main transcriptc.675+257C>G intron_variant XP_016856810.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MPZENST00000533357.5 linkuse as main transcriptc.*25C>G 3_prime_UTR_variant 6/61 NM_000530.8 ENSP00000432943 P1P25189-1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
6
AN:
146222
Hom.:
0
Cov.:
31
FAILED QC
Gnomad AFR
AF:
0.0000745
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000230
Gnomad SAS
AF:
0.000248
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000150
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00770
AC:
4154
AN:
539744
Hom.:
0
Cov.:
16
AF XY:
0.00669
AC XY:
1944
AN XY:
290406
show subpopulations
Gnomad4 AFR exome
AF:
0.00690
Gnomad4 AMR exome
AF:
0.000579
Gnomad4 ASJ exome
AF:
0.00460
Gnomad4 EAS exome
AF:
0.00355
Gnomad4 SAS exome
AF:
0.000965
Gnomad4 FIN exome
AF:
0.00203
Gnomad4 NFE exome
AF:
0.0109
Gnomad4 OTH exome
AF:
0.00695
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000410
AC:
6
AN:
146352
Hom.:
0
Cov.:
31
AF XY:
0.0000420
AC XY:
3
AN XY:
71488
show subpopulations
Gnomad4 AFR
AF:
0.0000743
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000230
Gnomad4 SAS
AF:
0.000247
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000150
Gnomad4 OTH
AF:
0.00

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 providedclinical testingPreventionGenetics, part of Exact SciencesMay 24, 2024This 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

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.68
CADD
Benign
20
DANN
Benign
0.65

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs776448650; hg19: chr1-161275641; API