rs753432312
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5
The NM_001352754.2(ARMC9):c.1336C>T(p.Arg446Cys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,802 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R446H) has been classified as Uncertain significance.
Frequency
Consequence
NM_001352754.2 missense, splice_region
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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARMC9 | NM_001352754.2 | c.1336C>T | p.Arg446Cys | missense_variant, splice_region_variant | 15/25 | ENST00000611582.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARMC9 | ENST00000611582.5 | c.1336C>T | p.Arg446Cys | missense_variant, splice_region_variant | 15/25 | 5 | NM_001352754.2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251320Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135826
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461802Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 727202
GnomAD4 genome ? Cov.: 32
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 | - - |
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