16-81315142-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_022041.4(GAN):c.29C>G(p.Pro10Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000217 in 1,384,648 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P10S) has been classified as Uncertain significance.
Frequency
Consequence
NM_022041.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GAN | NM_022041.4 | c.29C>G | p.Pro10Arg | missense_variant | 1/11 | ENST00000648994.2 | |
GAN | NM_001377486.1 | c.-496C>G | 5_prime_UTR_variant | 1/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GAN | ENST00000648994.2 | c.29C>G | p.Pro10Arg | missense_variant | 1/11 | NM_022041.4 | P1 | ||
GAN | ENST00000674788.1 | n.154C>G | non_coding_transcript_exon_variant | 1/3 | |||||
GAN | ENST00000648349.2 | c.29C>G | p.Pro10Arg | missense_variant, NMD_transcript_variant | 1/10 | ||||
GAN | ENST00000650388.1 | c.29C>G | p.Pro10Arg | missense_variant, NMD_transcript_variant | 1/9 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.00000217 AC: 3AN: 1384648Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 685168
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Giant axonal neuropathy 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 12, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 645135). This variant has not been reported in the literature in individuals affected with GAN-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 10 of the GAN protein (p.Pro10Arg). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at