rs200201741
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PM5BP4
The NM_001134831.2(AHI1):c.989A>T(p.Asp330Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,814 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D330G) has been classified as Likely benign.
Frequency
Consequence
NM_001134831.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AHI1 | NM_001134831.2 | c.989A>T | p.Asp330Val | missense_variant | 9/29 | ENST00000265602.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AHI1 | ENST00000265602.11 | c.989A>T | p.Asp330Val | missense_variant | 9/29 | 1 | NM_001134831.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152164Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461650Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727108
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152164Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74340
ClinVar
Submissions by phenotype
Familial aplasia of the vermis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 27, 2021 | This sequence change replaces aspartic acid with valine at codon 330 of the AHI1 protein (p.Asp330Val). The aspartic acid residue is moderately conserved and there is a large physicochemical difference between aspartic acid and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with AHI1-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt AHI1 protein function. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at