2-231214912-C-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001352754.2(ARMC9):c.259C>T(p.Arg87Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,613,968 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. R87R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001352754.2 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARMC9 | NM_001352754.2 | c.259C>T | p.Arg87Ter | stop_gained | 4/25 | ENST00000611582.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARMC9 | ENST00000611582.5 | c.259C>T | p.Arg87Ter | stop_gained | 4/25 | 5 | NM_001352754.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152098Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251478Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135918
GnomAD4 exome AF: 0.0000178 AC: 26AN: 1461870Hom.: 0 Cov.: 30 AF XY: 0.0000165 AC XY: 12AN XY: 727236
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152098Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74302
ClinVar
Submissions by phenotype
ARMC9-related Joubert syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | research | UW Hindbrain Malformation Research Program, University of Washington | May 01, 2017 | - - |
Joubert syndrome 30 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 16, 2017 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 30, 2023 | This sequence change creates a premature translational stop signal (p.Arg87*) in the ARMC9 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ARMC9 are known to be pathogenic (PMID: 28625504). This variant is present in population databases (no rsID available, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with Joubert syndrome (PMID: 28625504). ClinVar contains an entry for this variant (Variation ID: 427933). For these reasons, this variant has been classified as Pathogenic. - |
Familial aplasia of the vermis Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | University of Washington Center for Mendelian Genomics, University of Washington | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at