chr3-52394642-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_015512.5(DNAH1):c.10804G>A(p.Asp3602Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000513 in 1,579,902 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D3602E) 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 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH1 | NM_015512.5 | c.10804G>A | p.Asp3602Asn | missense_variant | 67/78 | ENST00000420323.7 | |
DNAH1 | XM_017006129.2 | c.10873G>A | p.Asp3625Asn | missense_variant | 69/80 | ||
DNAH1 | XM_017006130.2 | c.10804G>A | p.Asp3602Asn | missense_variant | 68/79 | ||
DNAH1 | XM_017006131.2 | c.10747G>A | p.Asp3583Asn | missense_variant | 68/79 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH1 | ENST00000420323.7 | c.10804G>A | p.Asp3602Asn | missense_variant | 67/78 | 1 | NM_015512.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152178Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000226 AC: 5AN: 220870Hom.: 0 AF XY: 0.0000256 AC XY: 3AN XY: 117284
GnomAD4 exome AF: 0.0000504 AC: 72AN: 1427606Hom.: 0 Cov.: 32 AF XY: 0.0000511 AC XY: 36AN XY: 705182
GnomAD4 genome AF: 0.0000591 AC: 9AN: 152296Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74456
ClinVar
Submissions by phenotype
Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2021 | This sequence change replaces aspartic acid with asparagine at codon 3602 of the DNAH1 protein (p.Asp3602Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs377385985, ExAC 0.003%). 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: "Probably 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