chr21-42475919-ACTC-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_080860.4(RSPH1):c.853_855del(p.Glu285del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000218 in 1,607,900 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000068 ( 0 hom., cov: 28)
Exomes 𝑓: 0.00023 ( 0 hom. )
Consequence
RSPH1
NM_080860.4 inframe_deletion
NM_080860.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.915
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 Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
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Nonframeshift variant in NON repetitive region in NM_080860.4. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RSPH1 | NM_080860.4 | c.853_855del | p.Glu285del | inframe_deletion | 8/9 | ENST00000291536.8 | |
RSPH1 | NM_001286506.2 | c.739_741del | p.Glu247del | inframe_deletion | 7/8 | ||
RSPH1 | XM_005261208.3 | c.646_648del | p.Glu216del | inframe_deletion | 6/7 | ||
RSPH1 | XM_011529786.2 | c.781_783del | p.Glu261del | inframe_deletion | 7/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RSPH1 | ENST00000291536.8 | c.853_855del | p.Glu285del | inframe_deletion | 8/9 | 1 | NM_080860.4 | P1 | |
RSPH1 | ENST00000398352.3 | c.739_741del | p.Glu247del | inframe_deletion | 7/8 | 5 | |||
RSPH1 | ENST00000493019.1 | n.2471_2473del | non_coding_transcript_exon_variant | 7/8 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000685 AC: 10AN: 145944Hom.: 0 Cov.: 28
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GnomAD3 exomes AF: 0.000111 AC: 28AN: 251428Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135892
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GnomAD4 exome AF: 0.000233 AC: 341AN: 1461836Hom.: 0 AF XY: 0.000237 AC XY: 172AN XY: 727228
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GnomAD4 genome ? AF: 0.0000685 AC: 10AN: 146064Hom.: 0 Cov.: 28 AF XY: 0.0000988 AC XY: 7AN XY: 70832
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 09, 2022 | This variant, c.853_855del, results in the deletion of 1 amino acid(s) of the RSPH1 protein (p.Glu285del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs562822292, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with RSPH1-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at