chrX-49249227-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_014008.5(CCDC22):c.1600C>T(p.Arg534Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000181 in 1,208,095 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 73 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_014008.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCDC22 | NM_014008.5 | c.1600C>T | p.Arg534Trp | missense_variant | 14/17 | ENST00000376227.4 | |
CCDC22 | XM_005272599.5 | c.1597C>T | p.Arg533Trp | missense_variant | 14/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC22 | ENST00000376227.4 | c.1600C>T | p.Arg534Trp | missense_variant | 14/17 | 1 | NM_014008.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000536 AC: 6AN: 112008Hom.: 0 Cov.: 23 AF XY: 0.0000293 AC XY: 1AN XY: 34184
GnomAD3 exomes AF: 0.0000110 AC: 2AN: 182571Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67453
GnomAD4 exome AF: 0.000194 AC: 213AN: 1096087Hom.: 0 Cov.: 32 AF XY: 0.000199 AC XY: 72AN XY: 361521
GnomAD4 genome ? AF: 0.0000536 AC: 6AN: 112008Hom.: 0 Cov.: 23 AF XY: 0.0000293 AC XY: 1AN XY: 34184
ClinVar
Submissions by phenotype
not specified Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jul 27, 2022 | Variant summary: CCDC22 c.1600C>T (p.Arg534Trp) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.1e-05 in 182571 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1600C>T in individuals affected with Ritscher-Schinzel Syndrome 2 and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted an assessment for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jan 22, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at