rs371637724
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001134831.2(AHI1):c.1516C>T(p.Arg506Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000143 in 1,605,334 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 Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. R506R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001134831.2 stop_gained
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 | UniProt |
---|---|---|---|---|---|---|---|
AHI1 | NM_001134831.2 | c.1516C>T | p.Arg506Ter | stop_gained | 12/29 | ENST00000265602.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AHI1 | ENST00000265602.11 | c.1516C>T | p.Arg506Ter | stop_gained | 12/29 | 1 | NM_001134831.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152182Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000161 AC: 4AN: 248910Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135022
GnomAD4 exome AF: 0.0000145 AC: 21AN: 1453152Hom.: 0 Cov.: 30 AF XY: 0.00000969 AC XY: 7AN XY: 722506
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74344
ClinVar
Submissions by phenotype
Joubert syndrome 3 Pathogenic:2
Pathogenic, criteria provided, single submitter | research | UW Hindbrain Malformation Research Program, University of Washington | Feb 23, 2015 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jan 03, 2022 | - - |
Familial aplasia of the vermis Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 04, 2023 | This sequence change creates a premature translational stop signal (p.Arg506*) in the AHI1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in AHI1 are known to be pathogenic (PMID: 15322546, 16453322, 28442542, 29186038). This variant is present in population databases (rs371637724, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with Joubert syndrome (PMID: 26092869). ClinVar contains an entry for this variant (Variation ID: 217534). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at