Genetic Variant CCT3:p.His4Tyr (chr1-156338175-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_005998.5(CCT3):c.10C>T(p.His4Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000441 in 1,588,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

CCT3
NM_005998.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.79

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 links:

TSACC (HGNC:30636): (TSSK6 activating cochaperone) Enables chaperone binding activity. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TSACC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18167645).

BS2

High AC in GnomAdExome4 at 5 AD gene.

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.10C>T	p.His4Tyr	missense	Exon 1 of 14	NP_005989.3
CCT3	NM_001008800.3		c.10C>T	p.His4Tyr	missense	Exon 1 of 12	NP_001008800.1	P49368-2
TSACC	NM_144627.5		c.-125+626G>A		intron	N/A	NP_653228.1	Q96A04

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCT3	ENST00000295688.8	TSL:1 MANE Select	c.10C>T	p.His4Tyr	missense	Exon 1 of 14	ENSP00000295688.3	P49368-1
CCT3	ENST00000533194.5	TSL:3	c.-31C>T		5_prime_UTR	Exon 1 of 5	ENSP00000434481.1	E9PQ35
TSACC	ENST00000368255.7	TSL:1	c.-125+626G>A		intron	N/A	ENSP00000357238.3	Q96A04

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000144

AC:

AN:

207902

AF XY:

0.00000901

show subpopulations

Gnomad AFR exome

AF:

0.000150

Gnomad AMR exome

AF:

0.0000361

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000348

AC:

AN:

1436254

Hom.:

Cov.:

AF XY:

0.00000281

AC XY:

AN XY:

711632

show subpopulations

African (AFR)

AF:

0.0000899

AC:

AN:

33378

American (AMR)

AF:

0.0000519

AC:

AN:

38558

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25438

East Asian (EAS)

AF:

0.00

AC:

AN:

38888

South Asian (SAS)

AF:

0.00

AC:

AN:

81772

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51558

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1101220

Other (OTH)

AF:

0.00

AC:

AN:

59718

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41448

American (AMR)

AF:

0.0000655

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000252

AC:

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

0.16

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.16

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.35

Eigen

Benign

0.042

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.027

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.76

MutationAssessor

Benign

0.97

PhyloP100

3.8

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.1

REVEL

Benign

0.13

Sift

Benign

0.23

Sift4G

Benign

1.0

Polyphen

0.035

Vest4

0.22

MutPred

0.37

Loss of disorder (P = 0.0322)

MVP

0.51

MPC

0.31

ClinPred

0.20

GERP RS

6.0

PromoterAI

-0.10

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.29

gMVP

0.37

Mutation Taster

=84/16

polymorphism

(source)

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over