rs369714206
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP3BP6
The NM_001369.3(DNAH5):c.13174T>C(p.Phe4392Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000452 in 1,614,148 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F4392C) 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.13174T>C | p.Phe4392Leu | missense_variant | 76/79 | ENST00000265104.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH5 | ENST00000265104.5 | c.13174T>C | p.Phe4392Leu | missense_variant | 76/79 | 1 | NM_001369.3 | P4 | |
DNAH5 | ENST00000681290.1 | c.13129T>C | p.Phe4377Leu | missense_variant | 76/79 | A1 | |||
DNAH5 | ENST00000683611.1 | n.507T>C | non_coding_transcript_exon_variant | 2/5 |
Frequencies
GnomAD3 genomes ? AF: 0.000223 AC: 34AN: 152160Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251348Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135848
GnomAD4 exome AF: 0.0000260 AC: 38AN: 1461870Hom.: 0 Cov.: 31 AF XY: 0.0000206 AC XY: 15AN XY: 727240
GnomAD4 genome ? AF: 0.000230 AC: 35AN: 152278Hom.: 0 Cov.: 32 AF XY: 0.000201 AC XY: 15AN XY: 74458
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:2Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 11, 2018 | The p.F4392L variant (also known as c.13174T>C), located in coding exon 76 of the DNAH5 gene, results from a T to C substitution at nucleotide position 13174. The phenylalanine at codon 4392 is replaced by leucine, an amino acid with highly similar properties. 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 alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at