rs878854459
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate
The NM_001369.3(DNAH5):c.9986T>C(p.Leu3329Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,860 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 Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. L3329L) has been classified as Likely benign.
Frequency
Consequence
NM_001369.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH5 | NM_001369.3 | c.9986T>C | p.Leu3329Pro | missense_variant | 59/79 | ENST00000265104.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH5 | ENST00000265104.5 | c.9986T>C | p.Leu3329Pro | missense_variant | 59/79 | 1 | NM_001369.3 | P4 | |
DNAH5 | ENST00000681290.1 | c.9941T>C | p.Leu3314Pro | missense_variant | 59/79 | A1 | |||
DNAH5 | ENST00000504001.3 | n.609+2869T>C | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461860Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727236
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Apr 25, 2023 | This missense change has been observed in individual(s) with primary ciliary dyskinesia (Invtiae). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DNAH5 protein function. ClinVar contains an entry for this variant (Variation ID: 238991). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 3329 of the DNAH5 protein (p.Leu3329Pro). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at