rs1553163206
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_017739.4(POMGNT1):c.1335del(p.Met446CysfsTer63) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
POMGNT1
NM_017739.4 frameshift
NM_017739.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.92
Genes affected
POMGNT1 (HGNC:19139): (protein O-linked mannose N-acetylglucosaminyltransferase 1 (beta 1,2-)) This gene encodes a type II transmembrane protein that resides in the Golgi apparatus. It participates in O-mannosyl glycosylation and is specific for alpha linked terminal mannose. Mutations in this gene may be associated with muscle-eye-brain disease and several congenital muscular dystrophies. Alternatively spliced transcript variants that encode different protein isoforms have been described. [provided by RefSeq, Feb 2014]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 1-46192385-TG-T is Pathogenic according to our data. Variant chr1-46192385-TG-T is described in ClinVar as [Pathogenic]. Clinvar id is 538743.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POMGNT1 | NM_017739.4 | c.1335del | p.Met446CysfsTer63 | frameshift_variant | 16/22 | ENST00000371984.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POMGNT1 | ENST00000371984.8 | c.1335del | p.Met446CysfsTer63 | frameshift_variant | 16/22 | 1 | NM_017739.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3;C3150417:Autosomal recessive limb-girdle muscular dystrophy type 2O Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 02, 2018 | This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Met446Cysfs*63) in the POMGNT1 gene. It is expected to result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with POMGNT1-related disease. ClinVar contains an entry for this variant (Variation ID: 538743). For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in POMGNT1 are known to be pathogenic (PMID: 19299310). - |
Computational scores
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Name
Calibrated prediction
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Prediction
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at