8-67154056-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001382391.1(CSPP1):c.2161C>T(p.Arg721Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000156 in 1,604,092 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R721G) has been classified as Uncertain significance.
Frequency
Consequence
NM_001382391.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CSPP1 | NM_001382391.1 | c.2161C>T | p.Arg721Trp | missense_variant | 19/31 | ENST00000678616.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CSPP1 | ENST00000678616.1 | c.2161C>T | p.Arg721Trp | missense_variant | 19/31 | NM_001382391.1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 151898Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 247800Hom.: 0 AF XY: 0.0000223 AC XY: 3AN XY: 134516
GnomAD4 exome AF: 0.0000145 AC: 21AN: 1452194Hom.: 0 Cov.: 26 AF XY: 0.0000166 AC XY: 12AN XY: 722956
GnomAD4 genome AF: 0.0000263 AC: 4AN: 151898Hom.: 0 Cov.: 32 AF XY: 0.0000405 AC XY: 3AN XY: 74156
ClinVar
Submissions by phenotype
Joubert syndrome 21 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 01, 2022 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 716 of the CSPP1 protein (p.Arg716Trp). This variant is present in population databases (rs778822396, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with CSPP1-related conditions. 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: "Deleterious"; PolyPhen-2: "Probably 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