rs397515622
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_130810.4(DNAAF4):c.325G>T(p.Glu109Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,718 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 (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_130810.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAAF4 | NM_130810.4 | c.325G>T | p.Glu109Ter | stop_gained | 4/10 | ENST00000321149.7 | |
DNAAF4-CCPG1 | NR_037923.1 | n.580G>T | non_coding_transcript_exon_variant | 3/16 | |||
DNAAF4 | NM_001033560.2 | c.325G>T | p.Glu109Ter | stop_gained | 4/9 | ||
DNAAF4 | NM_001033559.3 | c.325G>T | p.Glu109Ter | stop_gained | 4/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF4 | ENST00000321149.7 | c.325G>T | p.Glu109Ter | stop_gained | 4/10 | 1 | NM_130810.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461718Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 727164
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Dec 12, 2022 | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 23872636) - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Apr 07, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 68449). This premature translational stop signal has been observed in individual(s) with primary ciliary dyskinesia (PMID: 23872636). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu109*) in the DNAAF4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DNAAF4 are known to be pathogenic (PMID: 23872636). - |
Primary ciliary dyskinesia 25 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at