rs780427229
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_022041.4(GAN):c.1477G>A(p.Glu493Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,832 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 (★). Synonymous variant affecting the same amino acid position (i.e. E493E) has been classified as Likely benign.
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.1477G>A | p.Glu493Lys | missense_variant | 9/11 | ENST00000648994.2 | |
GAN | NM_001377486.1 | c.838G>A | p.Glu280Lys | missense_variant | 8/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GAN | ENST00000648994.2 | c.1477G>A | p.Glu493Lys | missense_variant | 9/11 | NM_022041.4 | P1 | ||
GAN | ENST00000567335.1 | n.35G>A | non_coding_transcript_exon_variant | 1/2 | 3 | ||||
GAN | ENST00000648349.2 | c.*1185G>A | 3_prime_UTR_variant, NMD_transcript_variant | 8/10 | |||||
GAN | ENST00000650388.1 | c.*834G>A | 3_prime_UTR_variant, NMD_transcript_variant | 7/9 |
Frequencies
GnomAD3 genomes ? Cov.: 30
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251492Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135922
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461832Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727232
GnomAD4 genome ? Cov.: 30
ClinVar
Submissions by phenotype
Giant axonal neuropathy 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 28, 2023 | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 533935). This missense change has been observed in individuals with giant axonal neuropathy (PMID: 30532362, 31655922). This variant is present in population databases (rs780427229, gnomAD 0.002%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 493 of the GAN protein (p.Glu493Lys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at