6-159779213-T-TG

Position:

• chr6-159779213-T-TG

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_030752.3(TCP1):​c.1502dupC​(p.Gly502fs) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TCP1 NM_030752.3 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.47

Genes affected

TCP1 (HGNC:11655): (t-complex 1) The protein encoded by this gene is a molecular chaperone that is a member of the chaperonin containing TCP1 complex (CCT), also known as the TCP1 ring complex (TRiC). This complex consists of two identical stacked rings, each containing eight different proteins. Unfolded polypeptides enter the central cavity of the complex and are folded in an ATP-dependent manner. The complex folds various proteins, including actin and tubulin. Alternate transcriptional splice variants of this gene, encoding different isoforms, have been characterized. In addition, three pseudogenes that appear to be derived from this gene have been found. [provided by RefSeq, Jun 2010]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.101 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCP1	NM_030752.3	c.1502dupC	p.Gly502fs	frameshift_variant	12/12	ENST00000321394.12	NP_110379.2
TCP1	NM_001008897.2	c.1037dupC	p.Gly347fs	frameshift_variant	11/11		NP_001008897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCP1	ENST00000321394.12	c.1502dupC	p.Gly502fs	frameshift_variant	12/12	1	NM_030752.3	ENSP00000317334.7
TCP1	ENST00000392168.6	c.1037dupC	p.Gly347fs	frameshift_variant	11/11	5		ENSP00000376008.2
TCP1	ENST00000544255.5	c.830dupC	p.Gly278fs	frameshift_variant	8/8	5		ENSP00000439447.1
TCP1	ENST00000420894	c.*36dupC		3_prime_UTR_variant	11/11	5		ENSP00000390159.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

INTELLECTUAL DEVELOPMENTAL DISORDER WITH POLYMICROGYRIA AND SEIZURES Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 10, 2025

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-160200245;