Genetic Variant CCT6B:p.Ala433Asp (chr17-34932416-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_006584.4(CCT6B):c.1298C>A(p.Ala433Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000049 in 1,612,048 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

CCT6B
NM_006584.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.24

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCT6B	NM_006584.4 link	c.1298C>A	p.Ala433Asp	missense_variant	Exon 11 of 14	ENST00000314144.10	NP_006575.2	Q92526-1
CCT6B	NM_001193529.3 link	c.1187C>A	p.Ala396Asp	missense_variant	Exon 10 of 13		NP_001180458.1	Q92526-3
CCT6B	NM_001193530.2 link	c.1163C>A	p.Ala388Asp	missense_variant	Exon 10 of 13		NP_001180459.1	Q92526-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CCT6B	ENST00000314144.10 link	c.1298C>A	p.Ala433Asp	missense_variant	Exon 11 of 14	1	NM_006584.4	ENSP00000327191.5	Q92526-1
CCT6B	ENST00000421975.7 link	c.1187C>A	p.Ala396Asp	missense_variant	Exon 10 of 13	1		ENSP00000398044.3	Q92526-3
CCT6B	ENST00000436961.7 link	c.1163C>A	p.Ala388Asp	missense_variant	Exon 10 of 13	2		ENSP00000400917.3	Q92526-2
CCT6B	ENST00000577307.1 link	n.2940C>A		non_coding_transcript_exon_variant	Exon 5 of 8	5

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000941

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000762

AC:

AN:

249226

AF XY:

0.0000816

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.0000296

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000267

AC:

AN:

1459842

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

726152

show subpopulations

African (AFR)

AF:

0.00102

AC:

AN:

33414

American (AMR)

AF:

0.0000675

AC:

AN:

44458

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26108

East Asian (EAS)

AF:

0.00

AC:

AN:

39618

South Asian (SAS)

AF:

0.00

AC:

AN:

85724

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53266

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111166

Other (OTH)

AF:

0.0000166

AC:

AN:

60324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000263

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.000941

AC:

AN:

41442

American (AMR)

AF:

0.0000655

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5208

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000864

Hom.:

Bravo

AF:

0.000329

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000741

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 06, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1298C>A (p.A433D) alteration is located in exon 11 (coding exon 11) of the CCT6B gene. This alteration results from a C to A substitution at nucleotide position 1298, causing the alanine (A) at amino acid position 433 to be replaced by an aspartic acid (D). 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

Uncertain

0.52

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Uncertain

0.020

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

.;T;.

Eigen

Benign

0.011

Eigen_PC

Benign

0.10

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.85

D;D;D

M_CAP

Benign

0.074

MetaRNN

Uncertain

0.44

T;T;T

MetaSVM

Benign

-0.35

MutationAssessor

Benign

1.7

.;L;.

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-4.5

D;D;D

REVEL

Uncertain

0.49

Sift

Uncertain

0.017

D;D;D

Sift4G

Uncertain

0.039

D;T;T

Polyphen

0.033

.;B;.

Vest4

0.72

MVP

0.65

MPC

0.14

ClinPred

0.11

GERP RS

3.7

Varity_R

0.79

gMVP

0.74

Mutation Taster

=33/67

disease causing

(source)

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

chr17-34932416-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over