rs749397968
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4BP6
The NM_001369.3(DNAH5):c.10195G>A(p.Val3399Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000378 in 1,613,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. V3399A) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH5 | NM_001369.3 | c.10195G>A | p.Val3399Ile | missense_variant | 60/79 | ENST00000265104.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH5 | ENST00000265104.5 | c.10195G>A | p.Val3399Ile | missense_variant | 60/79 | 1 | NM_001369.3 | P4 | |
DNAH5 | ENST00000681290.1 | c.10150G>A | p.Val3384Ile | missense_variant | 60/79 | A1 | |||
DNAH5 | ENST00000504001.3 | n.703G>A | non_coding_transcript_exon_variant | 5/5 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152228Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000108 AC: 27AN: 251102Hom.: 1 AF XY: 0.000111 AC XY: 15AN XY: 135680
GnomAD4 exome AF: 0.0000383 AC: 56AN: 1461754Hom.: 0 Cov.: 32 AF XY: 0.0000564 AC XY: 41AN XY: 727192
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152228Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74372
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1Benign:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 09, 2023 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 26, 2018 | The p.Val3399Ile variant in DNAH5 has not been previously reported in individua ls with primary ciliary dyskinesia, but has been identified in 0.06% (19/30778) of South Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gn omad.broadinstitute.org; dbSNP rs749397968). Computational prediction tools and conservation analysis suggest that the p.Val3399Ile variant may impact the prote in, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Val3399Ile variant is uncertain. ACMG/AMP Criteria applied: PP3. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at