9-36223473-G-A
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7
The NM_001128227.3(GNE):c.1404C>T(p.Phe468Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
GNE
NM_001128227.3 synonymous
NM_001128227.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.37
Publications
0 publications found
Genes affected
GNE (HGNC:23657): (glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase) The protein encoded by this gene is a bifunctional enzyme that initiates and regulates the biosynthesis of N-acetylneuraminic acid (NeuAc), a precursor of sialic acids. It is a rate-limiting enzyme in the sialic acid biosynthetic pathway. Sialic acid modification of cell surface molecules is crucial for their function in many biologic processes, including cell adhesion and signal transduction. Differential sialylation of cell surface molecules is also implicated in the tumorigenicity and metastatic behavior of malignant cells. Mutations in this gene are associated with sialuria, autosomal recessive inclusion body myopathy, and Nonaka myopathy. Alternative splicing of this gene results in transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
CLTA (HGNC:2090): (clathrin light chain A) Clathrin is a large, soluble protein composed of heavy and light chains. It functions as the main structural component of the lattice-type cytoplasmic face of coated pits and vesicles which entrap specific macromolecules during receptor-mediated endocytosis. This gene encodes one of two clathrin light chain proteins which are believed to function as regulatory elements. Alternative splicing results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 8 and 12. [provided by RefSeq, May 2010]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.38).
BP6
Variant 9-36223473-G-A is Benign according to our data. Variant chr9-36223473-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 460452.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=2.37 with no splicing effect.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| GNE | ENST00000396594.8 | c.1404C>T | p.Phe468Phe | synonymous_variant | Exon 8 of 12 | 1 | NM_001128227.3 | ENSP00000379839.3 | ||
| GNE | ENST00000642385.2 | c.1311C>T | p.Phe437Phe | synonymous_variant | Exon 8 of 12 | NM_005476.7 | ENSP00000494141.2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000343 AC: 5AN: 1458114Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 725658 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
5
AN:
1458114
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
725658
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:
33416
American (AMR)
AF:
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26120
East Asian (EAS)
AF:
AC:
0
AN:
39690
South Asian (SAS)
AF:
AC:
0
AN:
86166
European-Finnish (FIN)
AF:
AC:
0
AN:
53408
Middle Eastern (MID)
AF:
AC:
0
AN:
5312
European-Non Finnish (NFE)
AF:
AC:
5
AN:
1109058
Other (OTH)
AF:
AC:
0
AN:
60224
⚠️ 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: 0.245
Heterozygous variant carriers
0
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2
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4
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
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8
10
<30
30-35
35-40
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Sialuria;C1853926:GNE myopathy Benign:1
Jul 21, 2021
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
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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