rs1554668704
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_001128227.3(GNE):c.3G>A(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.000000685 in 1,460,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
GNE
NM_001128227.3 start_lost
NM_001128227.3 start_lost
Scores
2
7
4
Clinical Significance
Conservation
PhyloP100: 3.80
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 made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNE | NM_001128227.3 | c.3G>A | p.Met1? | start_lost | 1/12 | ENST00000396594.8 | |
LOC124902150 | XR_007061473.1 | n.297-7766C>T | intron_variant, non_coding_transcript_variant | ||||
GNE | XM_005251334.5 | c.3G>A | p.Met1? | start_lost | 1/11 | ||
GNE | NM_001190388.2 | c.-62G>A | 5_prime_UTR_variant | 1/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNE | ENST00000396594.8 | c.3G>A | p.Met1? | start_lost | 1/12 | 1 | NM_001128227.3 | ||
GNE | ENST00000543356.7 | c.-62G>A | 5_prime_UTR_variant | 1/11 | 1 | ||||
GNE | ENST00000644762.1 | n.35G>A | non_coding_transcript_exon_variant | 1/2 | |||||
CLTA | ENST00000464497.5 | c.*101+11368C>T | intron_variant, NMD_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460908Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 726784
GnomAD4 exome
AF:
AC:
1
AN:
1460908
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
726784
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
GNE myopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Nov 19, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationTaster
Benign
A;D
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Polyphen
P
Vest4
MutPred
Gain of catalytic residue at M1 (P = 0.0254);
MVP
ClinPred
D
GERP RS
gMVP
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at