rs775151697
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_015512.5(DNAH1):āc.9326G>Cā(p.Cys3109Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000118 in 1,612,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C3109R) has been classified as Uncertain significance.
Frequency
Consequence
NM_015512.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH1 | NM_015512.5 | c.9326G>C | p.Cys3109Ser | missense_variant | 58/78 | ENST00000420323.7 | |
DNAH1 | XM_017006129.2 | c.9395G>C | p.Cys3132Ser | missense_variant | 60/80 | ||
DNAH1 | XM_017006130.2 | c.9326G>C | p.Cys3109Ser | missense_variant | 59/79 | ||
DNAH1 | XM_017006131.2 | c.9395G>C | p.Cys3132Ser | missense_variant | 60/79 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH1 | ENST00000420323.7 | c.9326G>C | p.Cys3109Ser | missense_variant | 58/78 | 1 | NM_015512.5 | P1 | |
DNAH1 | ENST00000486752.5 | n.9587G>C | non_coding_transcript_exon_variant | 58/77 | 2 | ||||
DNAH1 | ENST00000488988.5 | n.916G>C | non_coding_transcript_exon_variant | 6/25 | 2 | ||||
DNAH1 | ENST00000490713.5 | c.26G>C | p.Cys9Ser | missense_variant, NMD_transcript_variant | 1/20 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152254Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000569 AC: 14AN: 245916Hom.: 0 AF XY: 0.0000524 AC XY: 7AN XY: 133670
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1460150Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9AN XY: 726298
GnomAD4 genome ? AF: 0.00000656 AC: 1AN: 152372Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74506
ClinVar
Submissions by phenotype
Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2021 | This sequence change replaces cysteine with serine at codon 3109 of the DNAH1 protein (p.Cys3109Ser). The cysteine residue is moderately conserved and there is a moderate physicochemical difference between cysteine and serine. This variant is present in population databases (rs775151697, ExAC 0.1%). This variant has not been reported in the literature in individuals affected with DNAH1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at