chr1-46193314-G-A
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_017739.4(POMGNT1):c.1101C>T(p.Arg367=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000626 in 1,613,594 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000064 ( 0 hom. )
Consequence
POMGNT1
NM_017739.4 synonymous
NM_017739.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.14
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 Benign. Variant got -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
Variant 1-46193314-G-A is Benign according to our data. Variant chr1-46193314-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 538739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-2.14 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POMGNT1 | NM_017739.4 | c.1101C>T | p.Arg367= | synonymous_variant | 12/22 | ENST00000371984.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POMGNT1 | ENST00000371984.8 | c.1101C>T | p.Arg367= | synonymous_variant | 12/22 | 1 | NM_017739.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152138Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000280 AC: 7AN: 250242Hom.: 0 AF XY: 0.0000370 AC XY: 5AN XY: 135258
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GnomAD4 exome AF: 0.0000643 AC: 94AN: 1461456Hom.: 0 Cov.: 33 AF XY: 0.0000619 AC XY: 45AN XY: 726976
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GnomAD4 genome AF: 0.0000460 AC: 7AN: 152138Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74330
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ClinVar
Significance: Likely benign
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Muscle eye brain disease Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3;C3150417:Autosomal recessive limb-girdle muscular dystrophy type 2O Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 20, 2024 | - - |
POMGNT1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 10, 2019 | 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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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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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