rs386834040
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_017739.4(POMGNT1):c.982dupG(p.Val328GlyfsTer11) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
POMGNT1
NM_017739.4 frameshift
NM_017739.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.03
Publications
3 publications found
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]
TSPAN1 (HGNC:20657): (tetraspanin 1) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 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 1-46193607-A-AC is Pathogenic according to our data. Variant chr1-46193607-A-AC is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 56611.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_017739.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| POMGNT1 | MANE Select | c.982dupG | p.Val328GlyfsTer11 | frameshift | Exon 11 of 22 | NP_060209.4 | Q8WZA1-1 | ||
| POMGNT1 | c.982dupG | p.Val328GlyfsTer11 | frameshift | Exon 11 of 23 | NP_001230695.2 | Q8WZA1-2 | |||
| POMGNT1 | c.982dupG | p.Val328GlyfsTer11 | frameshift | Exon 11 of 22 | NP_001397712.1 | A0A8I5KNB7 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| POMGNT1 | TSL:1 MANE Select | c.982dupG | p.Val328GlyfsTer11 | frameshift | Exon 11 of 22 | ENSP00000361052.3 | Q8WZA1-1 | ||
| POMGNT1 | TSL:2 | c.982dupG | p.Val328GlyfsTer11 | frameshift | Exon 11 of 23 | ENSP00000361060.1 | Q8WZA1-2 | ||
| POMGNT1 | c.982dupG | p.Val328GlyfsTer11 | frameshift | Exon 11 of 22 | ENSP00000508453.1 | A0A8I5KNB7 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD2 exomes AF: 0.00000796 AC: 2AN: 251212 AF XY: 0.00000737 show subpopulations
GnomAD2 exomes
AF:
AC:
2
AN:
251212
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461880Hom.: 0 Cov.: 92 AF XY: 0.00000138 AC XY: 1AN XY: 727242 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
1461880
Hom.:
Cov.:
92
AF XY:
AC XY:
1
AN XY:
727242
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
1
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86256
European-Finnish (FIN)
AF:
AC:
0
AN:
53412
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1112008
Other (OTH)
AF:
AC:
0
AN:
60396
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
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10
<30
30-35
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
ClinVar submissions
View on ClinVar Significance:Likely pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
2
-
-
Muscle eye brain disease (2)
1
-
-
Muscular dystrophy-dystroglycanopathy (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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