3-52359985-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_015512.5(DNAH1):c.4477A>G(p.Ile1493Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,613,822 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DNAH1 | NM_015512.5 | c.4477A>G | p.Ile1493Val | missense_variant | Exon 27 of 78 | ENST00000420323.7 | NP_056327.4 | |
DNAH1 | XM_017006129.2 | c.4477A>G | p.Ile1493Val | missense_variant | Exon 28 of 80 | XP_016861618.1 | ||
DNAH1 | XM_017006130.2 | c.4477A>G | p.Ile1493Val | missense_variant | Exon 28 of 79 | XP_016861619.1 | ||
DNAH1 | XM_017006131.2 | c.4477A>G | p.Ile1493Val | missense_variant | Exon 28 of 79 | XP_016861620.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152244Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461578Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727064
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152244Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74378
ClinVar
Submissions by phenotype
Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37 Uncertain:1
This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1493 of the DNAH1 protein (p.Ile1493Val). This variant is not present in population databases (gnomAD no frequency). 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: 544616). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt DNAH1 protein function with a positive predictive value of 80%. 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