6-43645196-T-C
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_152732.5(RSPH9):āc.98T>Cā(p.Met33Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000793 in 1,613,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_152732.5 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 |
---|---|---|---|---|---|---|---|---|
RSPH9 | NM_152732.5 | c.98T>C | p.Met33Thr | missense_variant | 1/5 | ENST00000372163.5 | NP_689945.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RSPH9 | ENST00000372163.5 | c.98T>C | p.Met33Thr | missense_variant | 1/5 | 1 | NM_152732.5 | ENSP00000361236 | P1 | |
RSPH9 | ENST00000372165.8 | c.98T>C | p.Met33Thr | missense_variant | 1/6 | 2 | ENSP00000361238 |
Frequencies
GnomAD3 genomes AF: 0.0000788 AC: 12AN: 152244Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 250482Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135830
GnomAD4 exome AF: 0.0000794 AC: 116AN: 1461604Hom.: 0 Cov.: 32 AF XY: 0.0000729 AC XY: 53AN XY: 727126
GnomAD4 genome AF: 0.0000788 AC: 12AN: 152244Hom.: 0 Cov.: 33 AF XY: 0.0000941 AC XY: 7AN XY: 74384
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 05, 2022 | This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 33 of the RSPH9 protein (p.Met33Thr). This variant is present in population databases (rs374043705, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with RSPH9-related conditions. ClinVar contains an entry for this variant (Variation ID: 575069). 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 threonine 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. - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 05, 2024 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at