rs746662023
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_001369.3(DNAH5):c.12209C>T(p.Thr4070Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000428 in 1,614,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001369.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH5 | NM_001369.3 | c.12209C>T | p.Thr4070Ile | missense_variant | 71/79 | ENST00000265104.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH5 | ENST00000265104.5 | c.12209C>T | p.Thr4070Ile | missense_variant | 71/79 | 1 | NM_001369.3 | P4 | |
DNAH5 | ENST00000681290.1 | c.12164C>T | p.Thr4055Ile | missense_variant | 71/79 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152154Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000215 AC: 54AN: 251282Hom.: 0 AF XY: 0.000140 AC XY: 19AN XY: 135798
GnomAD4 exome AF: 0.0000438 AC: 64AN: 1461848Hom.: 0 Cov.: 31 AF XY: 0.0000316 AC XY: 23AN XY: 727234
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152154Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74310
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 11, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
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 | Sep 16, 2015 | Variant classified as Uncertain Significance - Favor Benign. The p.Thr40470Ile v ariant in DNAH5 has not been previously reported in individuals with pulmonary d isease, but has been identified in 0.15% (17/11564) of Latino chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org). Computatio nal prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, while the clinical significanc e of the p.Thr40470Ile variant is uncertain, its frequency suggests that it is m ore likely to be benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at