chr21-32602299-G-C
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_021254.4(CFAP298):āc.735C>Gā(p.Tyr245*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000057 in 1,613,936 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 (ā ).
Frequency
Consequence
NM_021254.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CFAP298 | ENST00000290155.8 | c.735C>G | p.Tyr245* | stop_gained | Exon 6 of 7 | 1 | NM_021254.4 | ENSP00000290155.3 | ||
CFAP298-TCP10L | ENST00000673807.1 | c.666+862C>G | intron_variant | Intron 5 of 7 | ENSP00000501088.1 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152226Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000796 AC: 20AN: 251370Hom.: 0 AF XY: 0.0000883 AC XY: 12AN XY: 135866
GnomAD4 exome AF: 0.0000582 AC: 85AN: 1461710Hom.: 0 Cov.: 31 AF XY: 0.0000660 AC XY: 48AN XY: 727172
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152226Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74372
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia 26 Pathogenic:1
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not provided Pathogenic:1
This sequence change creates a premature translational stop signal (p.Tyr245*) in the CFAP298 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 46 amino acid(s) of the CFAP298 protein. This variant is present in population databases (rs202094637, gnomAD 0.2%). This premature translational stop signal has been observed in individual(s) with primary ciliary dyskinesia (PMID: 24094744; Invitae). ClinVar contains an entry for this variant (Variation ID: 209002). For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at