chr2-231214858-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5
The NM_001352754.2(ARMC9):c.205G>A(p.Gly69Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,613,974 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001352754.2 missense
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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ARMC9 | NM_001352754.2 | c.205G>A | p.Gly69Arg | missense_variant | Exon 4 of 25 | ENST00000611582.5 | NP_001339683.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152110Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251438Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135884
GnomAD4 exome AF: 0.0000349 AC: 51AN: 1461864Hom.: 0 Cov.: 30 AF XY: 0.0000371 AC XY: 27AN XY: 727226
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152110Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74314
ClinVar
Submissions by phenotype
not provided Pathogenic:1Uncertain:1
- -
This sequence change replaces glycine with arginine at codon 69 of the ARMC9 protein (p.Gly69Arg). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs750247691, gnomAD 0.006%). This missense change has been observed in individual(s) with Joubert syndrome (PMID: 28625504). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 427930). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. -
ARMC9-related Joubert syndrome Pathogenic:1
- -
Joubert syndrome 30 Pathogenic:1
- -
Familial aplasia of the vermis Pathogenic:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at