16-81363872-A-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_022041.4(GAN):c.1165A>T(p.Ile389Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,611,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GAN | NM_022041.4 | c.1165A>T | p.Ile389Phe | missense_variant | 7/11 | ENST00000648994.2 | |
GAN | NM_001377486.1 | c.526A>T | p.Ile176Phe | missense_variant | 6/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GAN | ENST00000648994.2 | c.1165A>T | p.Ile389Phe | missense_variant | 7/11 | NM_022041.4 | P1 | ||
GAN | ENST00000648349.2 | c.*873A>T | 3_prime_UTR_variant, NMD_transcript_variant | 6/10 | |||||
GAN | ENST00000650388.1 | c.*522A>T | 3_prime_UTR_variant, NMD_transcript_variant | 5/9 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152220Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251470Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135906
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1459476Hom.: 0 Cov.: 30 AF XY: 0.00000964 AC XY: 7AN XY: 726316
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152220Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74366
ClinVar
Submissions by phenotype
Giant axonal neuropathy 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 19, 2022 | This sequence change replaces isoleucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 389 of the GAN protein (p.Ile389Phe). This variant is present in population databases (no rsID available, gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GAN-related conditions. ClinVar contains an entry for this variant (Variation ID: 465386). 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. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at