rs767853104
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP3_ModerateBP6
The NM_001369.3(DNAH5):c.3895G>T(p.Val1299Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000039 in 1,613,958 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. V1299V) 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.3895G>T | p.Val1299Phe | missense_variant | 25/79 | ENST00000265104.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH5 | ENST00000265104.5 | c.3895G>T | p.Val1299Phe | missense_variant | 25/79 | 1 | NM_001369.3 | P4 | |
ENST00000503244.2 | n.253+7377C>A | intron_variant, non_coding_transcript_variant | 4 | ||||||
DNAH5 | ENST00000681290.1 | c.3850G>T | p.Val1284Phe | missense_variant | 25/79 | A1 | |||
ENST00000637153.1 | n.213+7417C>A | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152160Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251114Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135694
GnomAD4 exome AF: 0.0000369 AC: 54AN: 1461798Hom.: 0 Cov.: 33 AF XY: 0.0000330 AC XY: 24AN XY: 727198
GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152160Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74322
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 14, 2023 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 13, 2016 | The p.Val1299Phe variant in DNAH5 has not been previously reported in individual s with pulmonary disease, but has been identified in 3/66688 of European chromos omes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs767853104). Computational prediction tools and conservation analysis sug gest that the p.Val1299Phe variant may impact the protein, though this informati on is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Val1299Phe variant is uncertain. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at