rs766323732
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PVS1PM2PP3PP5_Moderate
The NM_015512.5(DNAH1):c.5104C>T(p.Arg1702Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,640 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_015512.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH1 | NM_015512.5 | c.5104C>T | p.Arg1702Ter | stop_gained | 32/78 | ENST00000420323.7 | |
DNAH1 | XM_017006129.2 | c.5104C>T | p.Arg1702Ter | stop_gained | 33/80 | ||
DNAH1 | XM_017006130.2 | c.5104C>T | p.Arg1702Ter | stop_gained | 33/79 | ||
DNAH1 | XM_017006131.2 | c.5104C>T | p.Arg1702Ter | stop_gained | 33/79 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH1 | ENST00000420323.7 | c.5104C>T | p.Arg1702Ter | stop_gained | 32/78 | 1 | NM_015512.5 | P1 | |
DNAH1 | ENST00000486752.5 | n.5365C>T | non_coding_transcript_exon_variant | 32/77 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.0000281 AC: 7AN: 249220Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135206
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461640Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 727114
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Feb 14, 2019 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in DNAH1 are known to be pathogenic (PMID: 27573432, 27798045). This variant has not been reported in the literature in individuals with DNAH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 568905). This variant is present in population databases (rs766323732, ExAC 0.02%). This sequence change creates a premature translational stop signal (p.Arg1702*) in the DNAH1 gene. It is expected to result in an absent or disrupted protein product. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at