rs727503395
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_152732.5(RSPH9):c.824_825delinsAT(p.Met275Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M275I) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 33)
Consequence
RSPH9
NM_152732.5 missense
NM_152732.5 missense
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.27
Genes affected
RSPH9 (HGNC:21057): (radial spoke head component 9) This gene encodes a protein thought to be a component of the radial spoke head in motile cilia and flagella. Mutations in this gene are associated with primary ciliary dyskinesia 12. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Jul 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RSPH9 | NM_152732.5 | c.824_825delinsAT | p.Met275Asn | missense_variant | 5/5 | ENST00000372163.5 | |
RSPH9 | NM_001193341.2 | c.876_877delinsAT | p.His292_Ala293delinsGlnSer | missense_variant | 6/6 | ||
POLR1C | NM_001318876.2 | c.945+141671_945+141672delinsAT | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RSPH9 | ENST00000372163.5 | c.824_825delinsAT | p.Met275Asn | missense_variant | 5/5 | 1 | NM_152732.5 | P1 | |
RSPH9 | ENST00000372165.8 | c.876_877delinsAT | p.His292_Ala293delinsGlnSer | missense_variant | 6/6 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 30, 2013 | The His292_Ala293delinsGlnSer variant in RSPH9 has not been reported in individu als with pulmonary disease or in large population studies. This variant changes two adjacent bases leading to a replacement of Histidine (His) and Alanine (Ala) at positions 292-293 with Glutamine (Gln) and Serine (Ser).Computational analys es (biochemical amino acid properties, evolutionary conservation, AlignGVGD, Pol yPhen2, and SIFT) do not provide strong support for or against an impact to the protein based on either amino acid change. Of note, neither the His292Gln nor th e Ala293Ser variants have independently been reported in individuals with pulmon ary disease or in large population studies. In summary, additional studies are n eeded to fully assess the clinical significance of the His292_Ala293delinsGlnSer variant. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at