rs573456055
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM1BP4BS2_Supporting
The ENST00000533357.5(MPZ):āc.530A>Gā(p.Tyr177Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,942 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 Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y177H) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000533357.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MPZ | NM_000530.8 | c.530A>G | p.Tyr177Cys | missense_variant | 4/6 | ENST00000533357.5 | NP_000521.2 | |
MPZ | NM_001315491.2 | c.530A>G | p.Tyr177Cys | missense_variant | 4/6 | NP_001302420.1 | ||
MPZ | XM_017001321.3 | c.560A>G | p.Tyr187Cys | missense_variant | 4/6 | XP_016856810.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MPZ | ENST00000533357.5 | c.530A>G | p.Tyr177Cys | missense_variant | 4/6 | 1 | NM_000530.8 | ENSP00000432943 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 151932Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250866Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135630
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461894Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 727248
GnomAD4 genome AF: 0.0000395 AC: 6AN: 152048Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74338
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease, type I Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 10, 2020 | This variant has not been reported in the literature in individuals with MPZ-related disease. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant is present in population databases (rs573456055, ExAC 0.02%). This sequence change replaces tyrosine with cysteine at codon 177 of the MPZ protein (p.Tyr177Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at