chr16-81315130-CCGTGTCTGACCCTCAGCACGCCGCGCGTCTGCTGCGAG-C
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1
The NM_022041.4(GAN):c.20_57del(p.Val7AlafsTer43) variant causes a frameshift change. Variant has been reported in ClinVar as Uncertain significance (no stars). Synonymous variant affecting the same amino acid position (i.e. A6A) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Failed GnomAD Quality Control
Consequence
GAN
NM_022041.4 frameshift
NM_022041.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.64
Genes affected
GAN (HGNC:4137): (gigaxonin) This gene encodes a member of the cytoskeletal BTB/kelch (Broad-Complex, Tramtrack and Bric a brac) repeat family. The encoded protein plays a role in neurofilament architecture and is involved in mediating the ubiquitination and degradation of some proteins. Defects in this gene are a cause of giant axonal neuropathy (GAN). [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 79 pathogenic variants in the truncated region.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GAN | NM_022041.4 | c.20_57del | p.Val7AlafsTer43 | frameshift_variant | 1/11 | ENST00000648994.2 | |
GAN | NM_001377486.1 | c.-505_-468del | 5_prime_UTR_variant | 1/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GAN | ENST00000648994.2 | c.20_57del | p.Val7AlafsTer43 | frameshift_variant | 1/11 | NM_022041.4 | P1 | ||
GAN | ENST00000674788.1 | n.145_182del | non_coding_transcript_exon_variant | 1/3 | |||||
GAN | ENST00000648349.2 | c.20_57del | p.Val7AlafsTer541 | frameshift_variant, NMD_transcript_variant | 1/10 | ||||
GAN | ENST00000650388.1 | c.20_57del | p.Val7AlafsTer? | frameshift_variant, NMD_transcript_variant | 1/9 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 1AN: 151972Hom.: 0 Cov.: 33 FAILED QC
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GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000658 AC: 1AN: 151972Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74244
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Data not reliable, filtered out with message: AS_VQSR
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Giant axonal neuropathy 1 Uncertain:2
Uncertain significance, no assertion criteria provided | literature only | Inherited Neuropathy Consortium | - | - - |
Uncertain significance, no assertion criteria provided | literature only | Inherited Neuropathy Consortium Ii, University Of Miami | Jan 06, 2016 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at