rs562263699
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_015512.5(DNAH1):c.10895G>A(p.Arg3632His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000255 in 1,612,606 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. R3632C) 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.10895G>A | p.Arg3632His | missense_variant | 68/78 | ENST00000420323.7 | |
DNAH1 | XM_017006129.2 | c.10964G>A | p.Arg3655His | missense_variant | 70/80 | ||
DNAH1 | XM_017006130.2 | c.10895G>A | p.Arg3632His | missense_variant | 69/79 | ||
DNAH1 | XM_017006131.2 | c.10838G>A | p.Arg3613His | missense_variant | 69/79 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH1 | ENST00000420323.7 | c.10895G>A | p.Arg3632His | missense_variant | 68/78 | 1 | NM_015512.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 152198Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000894 AC: 22AN: 245988Hom.: 0 AF XY: 0.0000748 AC XY: 10AN XY: 133618
GnomAD4 exome AF: 0.000270 AC: 394AN: 1460408Hom.: 0 Cov.: 32 AF XY: 0.000270 AC XY: 196AN XY: 726366
GnomAD4 genome ? AF: 0.000112 AC: 17AN: 152198Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74354
ClinVar
Submissions by phenotype
Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 03, 2022 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 3632 of the DNAH1 protein (p.Arg3632His). This variant is present in population databases (rs562263699, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of primary ciliary dyskinesia (Invitae). ClinVar contains an entry for this variant (Variation ID: 478391). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DNAH1 protein function. 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. - |
Spermatogenic failure 18 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Mar 26, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at