1-156310994-G-C

Variant names:

• chr1-156310994-G-C
• rs867280074
• NM_005998.5:c.1357C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005998.5(CCT3):​c.1357C>G​(p.Gln453Glu) variant causes a missense 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCT3 NM_005998.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.54

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCT3	NM_005998.5	c.1357C>G	p.Gln453Glu	missense_variant	Exon 12 of 14	ENST00000295688.8	NP_005989.3
CCT3	NM_001008800.3	c.1243C>G	p.Gln415Glu	missense_variant	Exon 10 of 12		NP_001008800.1
CCT3	NR_036564.2	n.1627C>G		non_coding_transcript_exon_variant	Exon 13 of 15
CCT3	NR_036565.2	n.1578C>G		non_coding_transcript_exon_variant	Exon 13 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCT3	ENST00000295688.8	c.1357C>G	p.Gln453Glu	missense_variant	Exon 12 of 14	1	NM_005998.5	ENSP00000295688.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1357C>G (p.Q453E) alteration is located in exon 12 (coding exon 12) of the CCT3 gene. This alteration results from a C to G substitution at nucleotide position 1357, causing the glutamine (Q) at amino acid position 453 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Uncertain	0.66	D;.;T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.70	D;D;D
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	0.73	N;.;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-2.8	D;D;D
REVEL	Uncertain	0.37
Sift	Benign	0.37	T;T;T
Sift4G	Benign	0.56	T;T;T
Polyphen		0.18	B;B;.
Vest4		0.71
MutPred		0.54		Loss of MoRF binding (P = 0.0422);.;.;
MVP		0.65
MPC		0.85
ClinPred		0.94	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.79
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs867280074; hg19: chr1-156280785;