rs587777059
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_080860.4(RSPH1):c.407_410del(p.Lys136MetfsTer6) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
RSPH1
NM_080860.4 frameshift
NM_080860.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.12
Genes affected
RSPH1 (HGNC:12371): (radial spoke head component 1) This gene encodes a male meiotic metaphase chromosome-associated acidic protein. This gene is expressed in tissues with motile cilia or flagella, including the trachea, lungs, airway brushings, and testes. Mutations in this gene result in primary ciliary dyskinesia-24. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2014]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 21-42485759-ATACT-A is Pathogenic according to our data. Variant chr21-42485759-ATACT-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 66989.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RSPH1 | NM_080860.4 | c.407_410del | p.Lys136MetfsTer6 | frameshift_variant | 5/9 | ENST00000291536.8 | |
RSPH1 | NM_001286506.2 | c.293_296del | p.Lys98MetfsTer6 | frameshift_variant | 4/8 | ||
RSPH1 | XM_005261208.3 | c.200_203del | p.Lys67MetfsTer6 | frameshift_variant | 3/7 | ||
RSPH1 | XM_011529786.2 | c.407_410del | p.Lys136MetfsTer6 | frameshift_variant | 5/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RSPH1 | ENST00000291536.8 | c.407_410del | p.Lys136MetfsTer6 | frameshift_variant | 5/9 | 1 | NM_080860.4 | P1 | |
RSPH1 | ENST00000398352.3 | c.293_296del | p.Lys98MetfsTer6 | frameshift_variant | 4/8 | 5 | |||
RSPH1 | ENST00000493019.1 | n.1033_1036del | non_coding_transcript_exon_variant | 4/8 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251480Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135914
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GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461884Hom.: 0 AF XY: 0.0000138 AC XY: 10AN XY: 727246
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GnomAD4 genome ? Cov.: 32
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia 24 Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Sep 23, 2020 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 05, 2013 | - - |
Kartagener syndrome Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at