rs113742238
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001369.3(DNAH5):c.9230G>T(p.Arg3077Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000126 in 1,613,870 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R3077Q) 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.9230G>T | p.Arg3077Leu | missense_variant | 55/79 | ENST00000265104.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH5 | ENST00000265104.5 | c.9230G>T | p.Arg3077Leu | missense_variant | 55/79 | 1 | NM_001369.3 | P4 | |
DNAH5 | ENST00000681290.1 | c.9185G>T | p.Arg3062Leu | missense_variant | 55/79 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 152114Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000215 AC: 54AN: 250916Hom.: 0 AF XY: 0.000288 AC XY: 39AN XY: 135576
GnomAD4 exome AF: 0.000127 AC: 186AN: 1461638Hom.: 0 Cov.: 33 AF XY: 0.000177 AC XY: 129AN XY: 727126
GnomAD4 genome AF: 0.000112 AC: 17AN: 152232Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7AN XY: 74448
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 | Apr 21, 2016 | The p.R3077L variant (also known as c.9230G>T), located in coding exon 55 of the DNAH5 gene, results from a G to T substitution at nucleotide position 9230. The arginine at codon 3077 is replaced by leucine, an amino acid with dissimilar properties. This variant was previously reported in the SNPDatabase as rs113742238. Based on data from the 1000 Genomes Project, the T allele has an overall frequency of approximately 0.05% (1/2098) total alleles studied. The highest observed frequency was 0.51% (1/196) Tuscan alleles. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Primary ciliary dyskinesia 3 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 14, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 29, 2022 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at