16-81363906-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_022041.4(GAN):c.1199C>T(p.Thr400Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. T400S) 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GAN | NM_022041.4 | c.1199C>T | p.Thr400Ile | missense_variant | 7/11 | ENST00000648994.2 | |
GAN | NM_001377486.1 | c.560C>T | p.Thr187Ile | missense_variant | 6/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GAN | ENST00000648994.2 | c.1199C>T | p.Thr400Ile | missense_variant | 7/11 | NM_022041.4 | P1 | ||
GAN | ENST00000648349.2 | c.*907C>T | 3_prime_UTR_variant, NMD_transcript_variant | 6/10 | |||||
GAN | ENST00000650388.1 | c.*556C>T | 3_prime_UTR_variant, NMD_transcript_variant | 5/9 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251472Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135908
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461268Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726978
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Giant axonal neuropathy 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 01, 2021 | 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with GAN-related conditions. This variant is present in population databases (rs368571975, ExAC 0.001%). This sequence change replaces threonine with isoleucine at codon 400 of the GAN protein (p.Thr400Ile). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and isoleucine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at