rs752263023
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_080860.4(RSPH1):c.150C>A(p.Phe50Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000979 in 1,613,932 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/25 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_080860.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RSPH1 | NM_080860.4 | c.150C>A | p.Phe50Leu | missense_variant | 2/9 | ENST00000291536.8 | |
RSPH1 | XM_011529786.2 | c.150C>A | p.Phe50Leu | missense_variant | 2/8 | ||
RSPH1 | NM_001286506.2 | c.55-121C>A | intron_variant | ||||
RSPH1 | XM_005261208.3 | c.67+3136C>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RSPH1 | ENST00000291536.8 | c.150C>A | p.Phe50Leu | missense_variant | 2/9 | 1 | NM_080860.4 | P1 | |
RSPH1 | ENST00000398352.3 | c.55-121C>A | intron_variant | 5 | |||||
RSPH1 | ENST00000493019.1 | n.210C>A | non_coding_transcript_exon_variant | 2/8 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000592 AC: 9AN: 152098Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000596 AC: 15AN: 251478Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135914
GnomAD4 exome AF: 0.000102 AC: 149AN: 1461834Hom.: 1 Cov.: 31 AF XY: 0.000106 AC XY: 77AN XY: 727214
GnomAD4 genome ? AF: 0.0000592 AC: 9AN: 152098Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5AN XY: 74278
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 24, 2021 | This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 50 of the RSPH1 protein (p.Phe50Leu). This variant is present in population databases (rs752263023, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with RSPH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 525456). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at