3-52326295-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_015512.5(DNAH1):āc.562C>Gā(p.Arg188Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000808 in 1,608,830 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 (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R188H) 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 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH1 | NM_015512.5 | c.562C>G | p.Arg188Gly | missense_variant | 4/78 | ENST00000420323.7 | |
DNAH1 | XM_017006129.2 | c.562C>G | p.Arg188Gly | missense_variant | 5/80 | ||
DNAH1 | XM_017006130.2 | c.562C>G | p.Arg188Gly | missense_variant | 5/79 | ||
DNAH1 | XM_017006131.2 | c.562C>G | p.Arg188Gly | missense_variant | 5/79 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH1 | ENST00000420323.7 | c.562C>G | p.Arg188Gly | missense_variant | 4/78 | 1 | NM_015512.5 | P1 | |
DNAH1 | ENST00000486752.5 | n.823C>G | non_coding_transcript_exon_variant | 4/77 | 2 | ||||
DNAH1 | ENST00000497875.1 | n.727C>G | non_coding_transcript_exon_variant | 5/21 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152212Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000687 AC: 10AN: 1456618Hom.: 0 Cov.: 31 AF XY: 0.00000828 AC XY: 6AN XY: 724758
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74360
ClinVar
Submissions by phenotype
Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 2022 | This variant has not been reported in the literature in individuals affected with DNAH1-related conditions. 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. 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"). ClinVar contains an entry for this variant (Variation ID: 544630). This variant is present in population databases (rs368210345, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 188 of the DNAH1 protein (p.Arg188Gly). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at