2-231296244-AGAT-A
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP3
The NM_001352754.2(ARMC9):βc.1770_1772delβ(p.Asp590del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00000479 in 1,460,886 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β β ). Synonymous variant affecting the same amino acid position (i.e. D589D) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Exomes π: 0.0000048 ( 0 hom. )
Consequence
ARMC9
NM_001352754.2 inframe_deletion
NM_001352754.2 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.60
Genes affected
ARMC9 (HGNC:20730): (armadillo repeat containing 9) Predicted to be involved in cilium assembly and positive regulation of smoothened signaling pathway. Located in centriole and ciliary basal body. Implicated in Joubert syndrome 30. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP3
Nonframeshift variant in repetitive region in NM_001352754.2
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARMC9 | NM_001352754.2 | c.1770_1772del | p.Asp590del | inframe_deletion | 19/25 | ENST00000611582.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARMC9 | ENST00000611582.5 | c.1770_1772del | p.Asp590del | inframe_deletion | 19/25 | 5 | NM_001352754.2 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1460886Hom.: 0 AF XY: 0.00000550 AC XY: 4AN XY: 726756
GnomAD4 exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
Bravo
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
ARMC9-related Joubert syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | Mar 05, 2018 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 08, 2022 | 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with ARMC9-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.1770_1772del, results in the deletion of 1 amino acid(s) of the ARMC9 protein (p.Asp590del), but otherwise preserves the integrity of the reading frame. - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at