chr18-33607606-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_030632.3(ASXL3):c.67C>T(p.His23Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000315 in 1,585,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_030632.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ASXL3 | NM_030632.3 | c.67C>T | p.His23Tyr | missense_variant | 2/12 | ENST00000269197.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ASXL3 | ENST00000269197.12 | c.67C>T | p.His23Tyr | missense_variant | 2/12 | 5 | NM_030632.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151900Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000955 AC: 2AN: 209390Hom.: 0 AF XY: 0.00000893 AC XY: 1AN XY: 111946
GnomAD4 exome AF: 0.00000279 AC: 4AN: 1433958Hom.: 0 Cov.: 30 AF XY: 0.00000563 AC XY: 4AN XY: 710614
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152018Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74320
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 06, 2024 | Variant summary: ATM c.67C>T (p.Arg23X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 2e-05 in 251364 control chromosomes. c.67C>T has been reported in the literature in individuals affected with Ataxia-Telangiectasia. These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at