6-159783941-CTCTG-C

Variant names:

• chr6-159783941-CTCTG-C
• NM_030752.3:c.793_796delCAGA

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_030752.3(TCP1):​c.793_796delCAGA​(p.Gln265GlufsTer22) variant causes a frameshift, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TCP1 NM_030752.3 frameshift, splice_region
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.52

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 Pathogenic. Variant got 11 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
• PP5: Variant 6-159783941-CTCTG-C is Pathogenic according to our data. Variant chr6-159783941-CTCTG-C is described in ClinVar as [Pathogenic]. Clinvar id is 3544399.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCP1	NM_030752.3	c.793_796delCAGA	p.Gln265GlufsTer22	frameshift_variant, splice_region_variant	Exon 7 of 12	ENST00000321394.12	NP_110379.2
TCP1	NM_001008897.2	c.328_331delCAGA	p.Gln110GlufsTer22	frameshift_variant, splice_region_variant	Exon 6 of 11		NP_001008897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCP1	ENST00000321394.12	c.793_796delCAGA	p.Gln265GlufsTer22	frameshift_variant, splice_region_variant	Exon 7 of 12	1	NM_030752.3	ENSP00000317334.7

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

INTELLECTUAL DEVELOPMENTAL DISORDER WITH POLYMICROGYRIA AND SEIZURES Pathogenic:1

Jan 10, 2025

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

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: chr6-160204973;