chrX-49242106-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_014008.5(CCDC22):c.319C>T(p.Arg107Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000082 in 1,097,673 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. 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 Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CCDC22 | NM_014008.5 | c.319C>T | p.Arg107Cys | missense_variant | Exon 3 of 17 | ENST00000376227.4 | NP_054727.1 | |
CCDC22 | XM_005272599.5 | c.319C>T | p.Arg107Cys | missense_variant | Exon 3 of 17 | XP_005272656.1 | ||
CCDC22 | XR_430506.4 | n.486C>T | non_coding_transcript_exon_variant | Exon 3 of 11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CCDC22 | ENST00000376227.4 | c.319C>T | p.Arg107Cys | missense_variant | Exon 3 of 17 | 1 | NM_014008.5 | ENSP00000365401.3 | ||
CCDC22 | ENST00000490300.1 | n.462C>T | non_coding_transcript_exon_variant | Exon 2 of 5 | 3 | |||||
CCDC22 | ENST00000496651.5 | n.410C>T | non_coding_transcript_exon_variant | Exon 3 of 6 | 3 |
Frequencies
GnomAD3 genomes Cov.: 22
GnomAD4 exome AF: 0.00000820 AC: 9AN: 1097673Hom.: 0 Cov.: 30 AF XY: 0.00000826 AC XY: 3AN XY: 363047
GnomAD4 genome Cov.: 22
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.319C>T (p.R107C) alteration is located in exon 3 (coding exon 3) of the CCDC22 gene. This alteration results from a C to T substitution at nucleotide position 319, causing the arginine (R) at amino acid position 107 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Ritscher-Schinzel syndrome 2 Uncertain:1
Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as 3B-VUS. Following criteria are met: 0105 - The mechanism of disease for this gene is not clearly established. However, loss-of-function is a likely mechanism of disease (PMIDs: 24916641, 23563313, 21826058). (N) 0109 - This gene is known to be associated with X-linked recessive disease. (N) 0200 - Variant is predicted to result in a missense amino acid change from arginine to cysteine (exon 3). (N) 0253 - Variant is hemizygous. (N) 0301 - Variant is absent from gnomAD. (P) 0502 - Missense variant with conflicting in silico predictions and/or uninformative conservation. (N) 0600 - Variant is located in an annotated domain or motif (DUF812 domain; NCBI, PDB). (N) 0705 - No comparable variants have previous evidence for pathogenicity. (N) 0807 - Variant has not previously been reported in a clinical context. (N) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant. (N) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at