5-10250350-A-G
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_012073.5(CCT5):āc.10A>Gā(p.Met4Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,970 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_012073.5 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 |
---|---|---|---|---|---|---|---|---|
CCT5 | NM_012073.5 | c.10A>G | p.Met4Val | missense_variant | 1/11 | ENST00000280326.9 | NP_036205.1 | |
CCT5 | NM_001306154.2 | c.10A>G | p.Met4Val | missense_variant | 1/10 | NP_001293083.1 | ||
CCT5 | NM_001306153.1 | c.42+305A>G | intron_variant | NP_001293082.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152198Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251102Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135876
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461772Hom.: 0 Cov.: 37 AF XY: 0.00000550 AC XY: 4AN XY: 727178
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152198Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2AN XY: 74358
ClinVar
Submissions by phenotype
Hereditary sensory and autonomic neuropathy with spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 30, 2021 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with CCT5-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 4 of the CCT5 protein (p.Met4Val). - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 27, 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