1-156311089-G-C

Position:

• chr1-156311089-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005998.5(CCT3):​c.1262C>G​(p.Ala421Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCT3 NM_005998.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.45

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37319577).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCT3	NM_005998.5	c.1262C>G	p.Ala421Gly	missense_variant	12/14	ENST00000295688.8
CCT3	NM_001008800.3	c.1148C>G	p.Ala383Gly	missense_variant	10/12
CCT3	NR_036564.2	n.1532C>G		non_coding_transcript_exon_variant	13/15
CCT3	NR_036565.2	n.1483C>G		non_coding_transcript_exon_variant	13/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCT3	ENST00000295688.8	c.1262C>G	p.Ala421Gly	missense_variant	12/14	1	NM_005998.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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

Dec 20, 2021

The c.1262C>G (p.A421G) alteration is located in exon 12 (coding exon 12) of the CCT3 gene. This alteration results from a C to G substitution at nucleotide position 1262, causing the alanine (A) at amino acid position 421 to be replaced by a glycine (G). 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	0.15
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.62	D;.;T
Eigen	Benign	-0.0051
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.2	M;.;.
MutationTaster	Benign	0.91	D;D;D;D
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.9	N;N;N
REVEL	Uncertain	0.31
Sift	Benign	0.45	T;T;T
Sift4G	Benign	0.54	T;T;T
Polyphen		0.0010	B;B;.
Vest4		0.48
MutPred		0.52		Gain of catalytic residue at A421 (P = 0.0169);.;.;
MVP		0.65
MPC		0.41
ClinPred		0.47	T
GERP RS		5.8
Varity_R		0.27
gMVP		0.35

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-156280880;