rs200553244
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001369.3(DNAH5):c.382G>A(p.Val128Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000256 in 1,614,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V128E) has been classified as Likely benign.
Frequency
Consequence
NM_001369.3 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 |
---|---|---|---|---|---|---|---|
DNAH5 | NM_001369.3 | c.382G>A | p.Val128Met | missense_variant | 4/79 | ENST00000265104.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH5 | ENST00000265104.5 | c.382G>A | p.Val128Met | missense_variant | 4/79 | 1 | NM_001369.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000256 AC: 39AN: 152154Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000143 AC: 36AN: 251388Hom.: 0 AF XY: 0.000147 AC XY: 20AN XY: 135858
GnomAD4 exome AF: 0.000257 AC: 375AN: 1461862Hom.: 0 Cov.: 31 AF XY: 0.000285 AC XY: 207AN XY: 727238
GnomAD4 genome ? AF: 0.000256 AC: 39AN: 152272Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74450
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:2Benign:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 11, 2022 | The p.V128M variant (also known as c.382G>A), located in coding exon 4 of the DNAH5 gene, results from a G to A substitution at nucleotide position 382. The valine at codon 128 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 27, 2019 | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Primary ciliary dyskinesia 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 01, 2017 | Likely pathogenicity based on finding it once in our laboratory in trans with a known pathogenic mutation in a 14-year-old female with chronic lung disease, AV malformations, chylopericardium and pulmonary lymphangiectasia, skin nevi, absent puberty. Heterozygotes are expected to be asymptomatic carriers. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at