rs141886699
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_080860.4(RSPH1):c.919C>T(p.Leu307Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 1,610,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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 Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RSPH1 | NM_080860.4 | c.919C>T | p.Leu307Phe | missense_variant | 9/9 | ENST00000291536.8 | |
RSPH1 | NM_001286506.2 | c.805C>T | p.Leu269Phe | missense_variant | 8/8 | ||
RSPH1 | XM_011529786.2 | c.847C>T | p.Leu283Phe | missense_variant | 8/8 | ||
RSPH1 | XM_005261208.3 | c.712C>T | p.Leu238Phe | missense_variant | 7/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RSPH1 | ENST00000291536.8 | c.919C>T | p.Leu307Phe | missense_variant | 9/9 | 1 | NM_080860.4 | P1 | |
RSPH1 | ENST00000398352.3 | c.805C>T | p.Leu269Phe | missense_variant | 8/8 | 5 | |||
RSPH1 | ENST00000493019.1 | n.2537C>T | non_coding_transcript_exon_variant | 8/8 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000467 AC: 71AN: 152154Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000175 AC: 44AN: 250970Hom.: 0 AF XY: 0.000177 AC XY: 24AN XY: 135620
GnomAD4 exome AF: 0.0000802 AC: 117AN: 1458038Hom.: 0 Cov.: 27 AF XY: 0.0000951 AC XY: 69AN XY: 725634
GnomAD4 genome ? AF: 0.000466 AC: 71AN: 152272Hom.: 0 Cov.: 33 AF XY: 0.000524 AC XY: 39AN XY: 74456
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 07, 2022 | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 307 of the RSPH1 protein (p.Leu307Phe). This variant is present in population databases (rs141886699, gnomAD 0.2%). 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: 454953). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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