Genetic Variant NM_005998.5:c.1357C>G (chr1-156310994-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.54

Publications

1 publications found

Variant links:

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

CCT3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCT3	NM_005998.5	MANE Select	c.1357C>G	p.Gln453Glu	missense	Exon 12 of 14	NP_005989.3
CCT3	NM_001008800.3		c.1243C>G	p.Gln415Glu	missense	Exon 10 of 12	NP_001008800.1	P49368-2
CCT3	NR_036564.2		n.1627C>G		non_coding_transcript_exon	Exon 13 of 15

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCT3	ENST00000295688.8	TSL:1 MANE Select	c.1357C>G	p.Gln453Glu	missense	Exon 12 of 14	ENSP00000295688.3	P49368-1
CCT3	ENST00000954294.1		c.1378C>G	p.Gln460Glu	missense	Exon 12 of 14	ENSP00000624353.1
CCT3	ENST00000898516.1		c.1372C>G	p.Gln458Glu	missense	Exon 12 of 14	ENSP00000568575.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Uncertain

0.070

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Uncertain

0.66

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.023

MetaRNN

Uncertain

0.70

MetaSVM

Benign

-0.62

MutationAssessor

Benign

0.73

PhyloP100

9.5

PrimateAI

Pathogenic

0.88

PROVEAN

Uncertain

-2.8

REVEL

Uncertain

0.37

Sift

Benign

0.37

Sift4G

Benign

0.56

Polyphen

0.18

Vest4

0.71

MutPred

0.54

Loss of MoRF binding (P = 0.0422)

MVP

0.65

MPC

0.85

ClinPred

0.94

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.79

gMVP

0.56

Mutation Taster

=12/88

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over