rs1554249521
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001010892.3(RSPH4A):c.1690C>T(p.Gln564Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001010892.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RSPH4A | NM_001010892.3 | c.1690C>T | p.Gln564Ter | stop_gained | 4/6 | ENST00000229554.10 | NP_001010892.1 | |
LOC124901386 | XR_007059721.1 | n.856G>A | non_coding_transcript_exon_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RSPH4A | ENST00000229554.10 | c.1690C>T | p.Gln564Ter | stop_gained | 4/6 | 1 | NM_001010892.3 | ENSP00000229554 | P1 | |
RSPH4A | ENST00000368581.8 | c.1663-841C>T | intron_variant | 1 | ENSP00000357570 | |||||
RSPH4A | ENST00000368580.4 | c.949C>T | p.Gln317Ter | stop_gained | 3/5 | 5 | ENSP00000357569 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248476Hom.: 0 AF XY: 0.00000743 AC XY: 1AN XY: 134512
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1459988Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726428
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 10, 2017 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in RSPH4A are known to be pathogenic (PMID: 19200523). This variant has not been reported in the literature in individuals with RSPH4A-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln564*) in the RSPH4A gene. It is expected to result in an absent or disrupted protein product. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at