Variant 21-29063363-GATATT-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2

The NM_006585.4(CCT8):c.925_929delAATAT(p.Asn309fs) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,312 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CCT8
NM_006585.4 frameshift

Scores

Not classified

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 8.83

Variant links:

Genes affected

CCT8 (HGNC:1623): (chaperonin containing TCP1 subunit 8) This gene encodes the theta subunit of the CCT chaperonin, which is abundant in the eukaryotic cytosol and may be involved in the transport and assembly of newly synthesized proteins. Alternative splicing results in multiple transcript variants of this gene. A pseudogene related to this gene is located on chromosome 1. [provided by RefSeq, Sep 2013]

CCT8 links:

CCT8 (HGNC:):

CCT8 links:

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 10 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCT8	NM_006585.4 linkuse as main transcript	c.925_929delAATAT	p.Asn309fs	frameshift_variant	8/15	ENST00000286788.9	NP_006576.2	P50990-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCT8	ENST00000286788.9 linkuse as main transcript	c.925_929delAATAT	p.Asn309fs	frameshift_variant	8/15	1	NM_006585.4	ENSP00000286788.4		P50990-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459312

Hom.:

AF XY:

0.00000138

AC XY:

AN XY:

725972

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Jan 09, 2025

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over