rs141945265
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_012472.6(DNAAF11):c.574C>T(p.Gln192Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,613,724 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_012472.6 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 |
---|---|---|---|---|---|---|---|
DNAAF11 | NM_012472.6 | c.574C>T | p.Gln192Ter | stop_gained | 5/12 | ENST00000620350.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF11 | ENST00000620350.5 | c.574C>T | p.Gln192Ter | stop_gained | 5/12 | 1 | NM_012472.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152048Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251390Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135870
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461676Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727152
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152048Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74252
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia 19 Pathogenic:2Other:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 20, 2023 | Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 39795). This premature translational stop signal has been observed in individual(s) with primary ciliary dyskinesia (PMID: 23122589). This variant is present in population databases (rs141945265, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Gln192*) in the LRRC6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LRRC6 are known to be pathogenic (PMID: 23122589). For these reasons, this variant has been classified as Pathogenic. - |
not provided, no classification provided | literature only | GeneReviews | - | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 02, 2012 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at