rs144575803
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP3BP6BS1BS2
The NM_001369.3(DNAH5):c.1198G>A(p.Val400Met) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00051 in 1,612,650 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001369.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH5 | NM_001369.3 | c.1198G>A | p.Val400Met | missense_variant, splice_region_variant | 10/79 | ENST00000265104.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH5 | ENST00000265104.5 | c.1198G>A | p.Val400Met | missense_variant, splice_region_variant | 10/79 | 1 | NM_001369.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000520 AC: 79AN: 152034Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000870 AC: 218AN: 250714Hom.: 1 AF XY: 0.000812 AC XY: 110AN XY: 135512
GnomAD4 exome AF: 0.000510 AC: 745AN: 1460498Hom.: 4 Cov.: 31 AF XY: 0.000537 AC XY: 390AN XY: 726578
GnomAD4 genome AF: 0.000513 AC: 78AN: 152152Hom.: 1 Cov.: 32 AF XY: 0.000578 AC XY: 43AN XY: 74392
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia 3 Uncertain:5
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | May 18, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Mar 29, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | May 18, 2021 | - - |
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, no assertion criteria provided | clinical testing | Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City | Jan 29, 2019 | - - |
Primary ciliary dyskinesia Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 02, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Dec 06, 2019 | - - |
DNAH5-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 09, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at