chr5-10250342-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PVS1_SupportingPM2
The NM_012073.5(CCT5):āc.2T>Gā(p.Met1?) variant causes a start lost change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_012073.5 start_lost
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CCT5 | NM_012073.5 | c.2T>G | p.Met1? | start_lost | Exon 1 of 11 | ENST00000280326.9 | NP_036205.1 | |
CCT5 | NM_001306154.2 | c.2T>G | p.Met1? | start_lost | Exon 1 of 10 | NP_001293083.1 | ||
CCT5 | NM_001306153.1 | c.42+297T>G | intron_variant | Intron 1 of 10 | NP_001293082.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251056Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135864
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461730Hom.: 0 Cov.: 37 AF XY: 0.00000825 AC XY: 6AN XY: 727156
GnomAD4 genome Cov.: 34
ClinVar
Submissions by phenotype
not provided Uncertain:1
The c.2T>G variant is predicted to cause a start-loss of the CCT5 gene due to a change of the methionine initiation codon. This variant has not been reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. The connection of CCT5 and hereditary sensory neuropathy with spastic paraplegia (MIM: 256840) is poorly understood at the present time. The HGMD database reports a single variant, the p.H147R, where it was shown to segregate in one Moroccan family with four affected homozygote siblings (Bouhouche, 2006). Since then, a single unaffected homozygote individual with p.H147R variant was reported by the Saudi Human Genome Program in an effort to uncover rare benign variants (Abouelhoda, 2016). The c.2T>G variant is listed in the Genome Aggregation Database (gnomAD) observed on a single chromosome out of 246,066. Given our current understanding, there is not enough evidence to classify the c.2T>G variant with certainty. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at