6-158977689-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_031924.8(RSPH3):c.1106G>A(p.Arg369Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000545 in 1,614,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_031924.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RSPH3 | NM_031924.8 | c.1106G>A | p.Arg369Gln | missense_variant | 8/8 | ENST00000367069.7 | NP_114130.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RSPH3 | ENST00000367069.7 | c.1106G>A | p.Arg369Gln | missense_variant | 8/8 | 1 | NM_031924.8 | ENSP00000356036 | P1 | |
RSPH3 | ENST00000449822.5 | c.818G>A | p.Arg273Gln | missense_variant | 6/6 | 2 | ENSP00000393195 |
Frequencies
GnomAD3 genomes AF: 0.000256 AC: 39AN: 152128Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000135 AC: 34AN: 251420Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135884
GnomAD4 exome AF: 0.0000335 AC: 49AN: 1461884Hom.: 0 Cov.: 32 AF XY: 0.0000275 AC XY: 20AN XY: 727244
GnomAD4 genome AF: 0.000256 AC: 39AN: 152246Hom.: 0 Cov.: 32 AF XY: 0.000255 AC XY: 19AN XY: 74466
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia 32 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Mar 08, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 511 of the RSPH3 protein (p.Arg511Gln). This variant is present in population databases (rs150432556, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with RSPH3-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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