chr2-73252817-C-T

Position:

• chr2-73252817-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006429.4(CCT7):​c.1588C>T​(p.Pro530Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCT7 NM_006429.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.36

Genes affected

CCT7 (HGNC:1622): (chaperonin containing TCP1 subunit 7) 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. Related pseudogenes have been identified on chromosomes 5 and 6. [provided by RefSeq, Oct 2009]

CCT7 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11335555).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCT7	NM_006429.4	c.1588C>T	p.Pro530Ser	missense_variant	12/12	ENST00000258091.10	NP_006420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCT7	ENST00000258091.10	c.1588C>T	p.Pro530Ser	missense_variant	12/12	1	NM_006429.4	ENSP00000258091.5
CCT7	ENST00000539919.5	c.1456C>T	p.Pro486Ser	missense_variant	13/13	2		ENSP00000437824.1
CCT7	ENST00000540468.5	c.1327C>T	p.Pro443Ser	missense_variant	10/10	2		ENSP00000442058.1
CCT7	ENST00000398422.2	c.976C>T	p.Pro326Ser	missense_variant	7/7	2		ENSP00000381456.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461802 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727208

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 17, 2023

The c.1588C>T (p.P530S) alteration is located in exon 12 (coding exon 12) of the CCT7 gene. This alteration results from a C to T substitution at nucleotide position 1588, causing the proline (P) at amino acid position 530 to be replaced by a serine (S). 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	Benign	0.066
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	.;.;T;.
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.76	T;T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.8	.;.;L;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.6	N;N;N;N
REVEL	Benign	0.036
Sift	Uncertain	0.028	D;D;D;D
Sift4G	Benign	0.064	T;D;T;T
Polyphen		0.14	.;.;B;.
Vest4		0.13
MutPred		0.23		.;.;Gain of glycosylation at P530 (P = 0.0376);.;
MVP		0.23
MPC		0.46
ClinPred		0.53	D
GERP RS		4.1
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
Varity_R		0.12
gMVP		0.71

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

Other links and lift over

dbSNP: rs1687657102; hg19: chr2-73479945;