rs775624344
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_015512.5(DNAH1):c.10150C>T(p.Arg3384Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,613,978 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R3384H) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH1 | NM_015512.5 | c.10150C>T | p.Arg3384Cys | missense_variant | 64/78 | ENST00000420323.7 | |
DNAH1 | XM_017006129.2 | c.10219C>T | p.Arg3407Cys | missense_variant | 66/80 | ||
DNAH1 | XM_017006130.2 | c.10150C>T | p.Arg3384Cys | missense_variant | 65/79 | ||
DNAH1 | XM_017006131.2 | c.10093C>T | p.Arg3365Cys | missense_variant | 65/79 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH1 | ENST00000420323.7 | c.10150C>T | p.Arg3384Cys | missense_variant | 64/78 | 1 | NM_015512.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152172Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000361 AC: 9AN: 249150Hom.: 0 AF XY: 0.0000666 AC XY: 9AN XY: 135202
GnomAD4 exome AF: 0.0000267 AC: 39AN: 1461688Hom.: 0 Cov.: 33 AF XY: 0.0000440 AC XY: 32AN XY: 727130
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152290Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5AN XY: 74472
ClinVar
Submissions by phenotype
Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 27, 2022 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 3384 of the DNAH1 protein (p.Arg3384Cys). This variant is present in population databases (rs775624344, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with DNAH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 478380). 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: "Possibly Damaging"; 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