Genetic Variant CCT6B:p.Gly525Trp (chr17-34928068-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_006584.4(CCT6B):c.1573G>T(p.Gly525Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,458,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G525R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CCT6B
NM_006584.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.53

Publications

0 publications found

Variant links:

Genes affected

CCT6B (HGNC:1621): (chaperonin containing TCP1 subunit 6B) This gene encodes 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]

CCT6B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.827

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006584.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCT6B	NM_006584.4	MANE Select	c.1573G>T	p.Gly525Trp	missense	Exon 14 of 14	NP_006575.2	Q92526-1
CCT6B	NM_001193529.3		c.1462G>T	p.Gly488Trp	missense	Exon 13 of 13	NP_001180458.1	Q92526-3
CCT6B	NM_001193530.2		c.1438G>T	p.Gly480Trp	missense	Exon 13 of 13	NP_001180459.1	Q92526-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCT6B	ENST00000314144.10	TSL:1 MANE Select	c.1573G>T	p.Gly525Trp	missense	Exon 14 of 14	ENSP00000327191.5	Q92526-1
CCT6B	ENST00000421975.7	TSL:1	c.1462G>T	p.Gly488Trp	missense	Exon 13 of 13	ENSP00000398044.3	Q92526-3
CCT6B	ENST00000436961.7	TSL:2	c.1438G>T	p.Gly480Trp	missense	Exon 13 of 13	ENSP00000400917.3	Q92526-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1458894

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725822

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33276

American (AMR)

AF:

0.00

AC:

AN:

44282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26076

East Asian (EAS)

AF:

0.00

AC:

AN:

39434

South Asian (SAS)

AF:

0.00

AC:

AN:

85806

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110604

Other (OTH)

AF:

0.00

AC:

AN:

60282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.040

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.63

Eigen

Pathogenic

0.98

Eigen_PC

Pathogenic

0.88

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.99

M_CAP

Uncertain

0.15

MetaRNN

Pathogenic

0.83

MetaSVM

Uncertain

0.55

MutationAssessor

Pathogenic

3.9

PhyloP100

5.5

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-7.3

REVEL

Uncertain

0.50

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.50

MutPred

0.83

Gain of MoRF binding (P = 0.0053)

MVP

0.70

MPC

0.47

ClinPred

1.0

GERP RS

5.2

Varity_R

0.84

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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