chr2-61873242-C-T

Variant names:

Variant summary

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

The NM_006430.4(CCT4):c.969G>A(p.Met323Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000432 in 1,390,036 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

CCT4
NM_006430.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.75

Publications

0 publications found

Variant links:

Genes affected

CCT4 (HGNC:1617): (chaperonin containing TCP1 subunit 4) The chaperonin containing TCP1 (MIM 186980) complex (CCT), also called the TCP1 ring complex, consists of 2 back-to-back rings, each containing 8 unique but homologous subunits, such as CCT4. CCT assists the folding of newly translated polypeptide substrates through multiple rounds of ATP-driven release and rebinding of partially folded intermediate forms. Substrates of CCT include the cytoskeletal proteins actin (see MIM 102560) and tubulin (see MIM 191130), as well as alpha-transducin (MIM 139330) (Won et al., 1998 [PubMed 9819444]).[supplied by OMIM, Mar 2008]

CCT4 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: G2P
neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

CCT4 links:

ENSG00000236498 (HGNC:):

ENSG00000236498 links:

Genome browser will be placed here

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
CCT4	NM_006430.4 link	c.969G>A	p.Met323Ile	missense_variant	Exon 9 of 14	ENST00000394440.8	NP_006421.2	P50991-1
CCT4	NM_001256721.1 link	c.879G>A	p.Met293Ile	missense_variant	Exon 8 of 13		NP_001243650.1	P50991-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCT4	ENST00000394440.8 link	c.969G>A	p.Met323Ile	missense_variant	Exon 9 of 14	1	NM_006430.4	ENSP00000377958.3		P50991-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000432

AC:

AN:

1390036

Hom.:

Cov.:

AF XY:

0.00000287

AC XY:

AN XY:

695704

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

31764

American (AMR)

AF:

0.00

AC:

AN:

44594

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25616

East Asian (EAS)

AF:

0.00

AC:

AN:

39390

South Asian (SAS)

AF:

0.00

AC:

AN:

84558

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5582

European-Non Finnish (NFE)

AF:

0.00000573

AC:

AN:

1047206

Other (OTH)

AF:

0.00

AC:

AN:

57946

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000056), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.333

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 08, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.969G>A (p.M323I) alteration is located in exon 9 (coding exon 9) of the CCT4 gene. This alteration results from a G to A substitution at nucleotide position 969, causing the methionine (M) at amino acid position 323 to be replaced by an isoleucine (I). 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

Pathogenic

0.73

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.16

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.48

T;.

Eigen

Uncertain

0.63

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Benign

0.019

MetaRNN

Uncertain

0.69

D;D

MetaSVM

Uncertain

-0.27

MutationAssessor

Benign

2.0

M;.

PhyloP100

7.8

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-2.0

N;N

REVEL

Uncertain

0.43

Sift

Benign

0.056

T;T

Sift4G

Uncertain

0.047

D;D

Polyphen

0.52

P;.

Vest4

0.86

MutPred

0.57

Gain of sheet (P = 0.0101);.;

MVP

0.30

MPC

0.84

ClinPred

0.85

GERP RS

5.8

Varity_R

0.75

gMVP

0.81

Mutation Taster

=7/93

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

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

chr2-61873242-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over