rs767196276
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_015512.5(DNAH1):c.12339G>A(p.Trp4113Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000112 in 1,613,932 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 Likely 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 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH1 | NM_015512.5 | c.12339G>A | p.Trp4113Ter | stop_gained | 76/78 | ENST00000420323.7 | |
DNAH1 | XM_017006129.2 | c.12408G>A | p.Trp4136Ter | stop_gained | 78/80 | ||
DNAH1 | XM_017006130.2 | c.12339G>A | p.Trp4113Ter | stop_gained | 77/79 | ||
DNAH1 | XM_017006131.2 | c.12282G>A | p.Trp4094Ter | stop_gained | 77/79 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH1 | ENST00000420323.7 | c.12339G>A | p.Trp4113Ter | stop_gained | 76/78 | 1 | NM_015512.5 | P1 | |
DNAH1 | ENST00000486752.5 | n.12796G>A | non_coding_transcript_exon_variant | 75/77 | 2 | ||||
DNAH1 | ENST00000488988.5 | n.4125G>A | non_coding_transcript_exon_variant | 23/25 | 2 | ||||
DNAH1 | ENST00000490713.5 | c.*121G>A | 3_prime_UTR_variant, NMD_transcript_variant | 18/20 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152232Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000283 AC: 7AN: 247618Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134510
GnomAD4 exome AF: 0.000123 AC: 180AN: 1461700Hom.: 0 Cov.: 31 AF XY: 0.000129 AC XY: 94AN XY: 727132
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152232Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74368
ClinVar
Submissions by phenotype
Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Apr 23, 2022 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 478374). This variant has not been reported in the literature in individuals affected with DNAH1-related conditions. This variant is present in population databases (rs767196276, gnomAD 0.006%). This sequence change creates a premature translational stop signal (p.Trp4113*) in the DNAH1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DNAH1 are known to be pathogenic (PMID: 27573432, 27798045). - |
DNAH1-related disorder Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 12, 2023 | The DNAH1 c.12339G>A variant is predicted to result in premature protein termination (p.Trp4113*). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0055% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-52433115-G-A). Nonsense variants in DNAH1 are expected to be pathogenic. This variant is interpreted as likely pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at