rs141828476
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001369.3(DNAH5):c.13448C>T(p.Thr4483Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000793 in 1,613,878 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T4483T) 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 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH5 | NM_001369.3 | c.13448C>T | p.Thr4483Met | missense_variant | 77/79 | ENST00000265104.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH5 | ENST00000265104.5 | c.13448C>T | p.Thr4483Met | missense_variant | 77/79 | 1 | NM_001369.3 | P4 | |
DNAH5 | ENST00000681290.1 | c.13403C>T | p.Thr4468Met | missense_variant | 77/79 | A1 | |||
DNAH5 | ENST00000683611.1 | n.781C>T | non_coding_transcript_exon_variant | 3/5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000658 AC: 10AN: 152040Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000716 AC: 18AN: 251362Hom.: 0 AF XY: 0.0000957 AC XY: 13AN XY: 135844
GnomAD4 exome AF: 0.0000807 AC: 118AN: 1461838Hom.: 0 Cov.: 34 AF XY: 0.000103 AC XY: 75AN XY: 727222
GnomAD4 genome ? AF: 0.0000658 AC: 10AN: 152040Hom.: 0 Cov.: 32 AF XY: 0.0000943 AC XY: 7AN XY: 74240
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 26, 2015 | The p.T4483M variant (also known as c.13448C>T), located in coding exon 77 of the DNAH5 gene, results from a C to T substitution at nucleotide position 13448. The threonine at codon 4483 is replaced by methionine, an amino acid with similar properties. This variant was previously reported in the SNPDatabase as rs141828476. Based on data from the NHLBI Exome Sequencing Project (ESP), the T allele has an overall frequency of approximately 0.02% (2/13006) total alleles studied, having been observed in 0.05% (2/4406) African American alleles. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2023 | DNAH5: PM2 - |
Primary ciliary dyskinesia 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at