rs863225131
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001134831.2(AHI1):āc.2495T>Gā(p.Leu832*) variant causes a stop gained, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,447,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely pathogenic (ā ā ). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001134831.2 stop_gained, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AHI1 | NM_001134831.2 | c.2495T>G | p.Leu832* | stop_gained, splice_region_variant | 19/29 | ENST00000265602.11 | NP_001128303.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AHI1 | ENST00000265602.11 | c.2495T>G | p.Leu832* | stop_gained, splice_region_variant | 19/29 | 1 | NM_001134831.2 | ENSP00000265602.6 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000207 AC: 3AN: 1447062Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1AN XY: 718676
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Joubert syndrome 3 Pathogenic:1
Pathogenic, criteria provided, single submitter | research | UW Hindbrain Malformation Research Program, University of Washington | Feb 23, 2015 | - - |
Joubert syndrome and related disorders Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jan 06, 2023 | Variant summary: AHI1 c.2495T>G (p.Leu832X) 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 in ClinVar and are associated with Joubert syndrome in HGMD. The variant was absent in 231274 control chromosomes. c.2495T>G has been reported in the literature in at least one individual affected with Joubert Syndrome (e.g., Parisi_2006). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One ClinVar submitter (evaluation after 2014) has cited the variant and classified it as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at