1-156311164-TG-T

Variant names:

• chr1-156311164-TG-T
• NM_005998.5:c.1186delC

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_005998.5(CCT3):​c.1186delC​(p.Gln396LysfsTer27) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCT3 NM_005998.5 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.54
• Publications: 0 publications found

Genes affected

CCT3 (HGNC:1616): (chaperonin containing TCP1 subunit 3) 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 have been characterized for this gene. In addition, a pseudogene of this gene has been found on chromosome 8. [provided by RefSeq, Aug 2010]

CCT3 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• neurodevelopmental disorder with speech or visual impairment and brain hypomyelination

  Inheritance: AD Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Pathogenic. The variant received 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 1-156311164-TG-T is Pathogenic according to our data. Variant chr1-156311164-TG-T is described in ClinVar as Pathogenic. ClinVar VariationId is 3544400.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005998.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCT3	NM_005998.5	MANE Select	c.1186delC	p.Gln396LysfsTer27	frameshift	Exon 12 of 14	NP_005989.3
	CCT3	NM_001008800.3		c.1072delC	p.Gln358LysfsTer27	frameshift	Exon 10 of 12	NP_001008800.1	P49368-2
	CCT3	NR_036564.2		n.1456delC		non_coding_transcript_exon	Exon 13 of 15

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCT3	ENST00000295688.8	TSL:1 MANE Select	c.1186delC	p.Gln396LysfsTer27	frameshift	Exon 12 of 14	ENSP00000295688.3	P49368-1
	CCT3	ENST00000954294.1		c.1207delC	p.Gln403LysfsTer27	frameshift	Exon 12 of 14	ENSP00000624353.1
	CCT3	ENST00000898516.1		c.1201delC	p.Gln401LysfsTer27	frameshift	Exon 12 of 14	ENSP00000568575.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Neurodevelopmental disorder with speech or visual impairment and brain hypomyelination (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Other links and lift over

hg19: chr1-156280955;