rs374909386
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1_ModeratePM2PP5_Very_Strong
The NM_017950.4(CCDC40):c.3354C>A(p.Tyr1118Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,613,670 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. Y1118Y) has been classified as Likely benign.
Frequency
Consequence
NM_017950.4 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 |
---|---|---|---|---|---|---|---|
CCDC40 | NM_017950.4 | c.3354C>A | p.Tyr1118Ter | stop_gained | 20/20 | ENST00000397545.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC40 | ENST00000397545.9 | c.3354C>A | p.Tyr1118Ter | stop_gained | 20/20 | 5 | NM_017950.4 | P2 | |
CCDC40 | ENST00000574799.5 | n.2891C>A | non_coding_transcript_exon_variant | 16/16 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152152Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000161 AC: 4AN: 249056Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135292
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461518Hom.: 0 Cov.: 36 AF XY: 0.00000963 AC XY: 7AN XY: 727052
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74322
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 23, 2022 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 195522). This premature translational stop signal has been observed in individual(s) with primary ciliary dyskinesia (Invitae). This variant is present in population databases (rs374909386, gnomAD 0.004%). This sequence change creates a premature translational stop signal (p.Tyr1118*) in the CCDC40 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 25 amino acid(s) of the CCDC40 protein. - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 06, 2014 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at