5-13780940-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4BP6
The NM_001369.3(DNAH5):c.8840C>T(p.Thr2947Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,613,628 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).
Frequency
Consequence
NM_001369.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNAH5 | ENST00000265104.5 | c.8840C>T | p.Thr2947Ile | missense_variant | Exon 53 of 79 | 1 | NM_001369.3 | ENSP00000265104.4 | ||
DNAH5 | ENST00000681290.1 | c.8795C>T | p.Thr2932Ile | missense_variant | Exon 53 of 79 | ENSP00000505288.1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152168Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000167 AC: 42AN: 250952Hom.: 0 AF XY: 0.000111 AC XY: 15AN XY: 135628
GnomAD4 exome AF: 0.0000356 AC: 52AN: 1461460Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18AN XY: 727042
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152168Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74328
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1Benign:2
- -
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. -
- -
not specified Uncertain:1
Variant classified as Uncertain Significance - Favor Benign. The p.Thr2947Ile va riant in DNAH5 has not been previously reported in individuals with pulmonary di sease, but has been identified in 0.14% (16/11474) of Latino chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org). Computation al prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, while the clinical significance of the p.Thr2947Ile variant is uncertain, its frequency suggests that it is mor e likely to be benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at