chr9-99217955-A-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_033087.4(ALG2):c.1230T>A(p.Tyr410Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,874 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. Y410Y) has been classified as Likely benign.
Frequency
Consequence
NM_033087.4 stop_gained
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALG2 | NM_033087.4 | c.1230T>A | p.Tyr410Ter | stop_gained | 2/2 | ENST00000476832.2 | |
ALG2 | XM_047423996.1 | c.951T>A | p.Tyr317Ter | stop_gained | 2/2 | ||
ALG2 | NR_024532.2 | n.1437T>A | non_coding_transcript_exon_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALG2 | ENST00000476832.2 | c.1230T>A | p.Tyr410Ter | stop_gained | 2/2 | 1 | NM_033087.4 | P1 | |
ALG2 | ENST00000319033.7 | c.951T>A | p.Tyr317Ter | stop_gained | 2/2 | 1 | |||
ALG2 | ENST00000238477.5 | c.*972T>A | 3_prime_UTR_variant, NMD_transcript_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251462Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135904
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461874Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727238
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
ALG2-congenital disorder of glycosylation;C4015597:Congenital myasthenic syndrome 14 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 27, 2022 | This variant is present in population databases (no rsID available, gnomAD 0.009%). This sequence change creates a premature translational stop signal (p.Tyr410*) in the ALG2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 7 amino acid(s) of the ALG2 protein. This variant has not been reported in the literature in individuals affected with ALG2-related conditions. 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at