rs768562044
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_022041.4(GAN):c.1148A>T(p.Asp383Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000924 in 1,611,688 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D383N) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GAN | NM_022041.4 | c.1148A>T | p.Asp383Val | missense_variant | 7/11 | ENST00000648994.2 | |
GAN | NM_001377486.1 | c.509A>T | p.Asp170Val | missense_variant | 6/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GAN | ENST00000648994.2 | c.1148A>T | p.Asp383Val | missense_variant | 7/11 | NM_022041.4 | P1 | ||
GAN | ENST00000648349.2 | c.*856A>T | 3_prime_UTR_variant, NMD_transcript_variant | 6/10 | |||||
GAN | ENST00000650388.1 | c.*505A>T | 3_prime_UTR_variant, NMD_transcript_variant | 5/9 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152182Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251452Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135896
GnomAD4 exome AF: 0.0000980 AC: 143AN: 1459506Hom.: 0 Cov.: 29 AF XY: 0.0000936 AC XY: 68AN XY: 726248
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74340
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 26, 2023 | The c.1148A>T (p.D383V) alteration is located in exon 7 (coding exon 7) of the GAN gene. This alteration results from a A to T substitution at nucleotide position 1148, causing the aspartic acid (D) at amino acid position 383 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Giant axonal neuropathy 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 06, 2022 | This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 383 of the GAN protein (p.Asp383Val). This variant is present in population databases (rs768562044, gnomAD 0.01%). 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: 533936). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Apr 11, 2023 | PM2 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at