Variant 6-159779645-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_030752.3(TCP1):c.1436A>G(p.Glu479Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000561 in 1,605,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TCP1
NM_030752.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.54

Variant links:

Genes affected

TCP1 (HGNC:11655): (t-complex 1) 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 of this gene, encoding different isoforms, have been characterized. In addition, three pseudogenes that appear to be derived from this gene have been found. [provided by RefSeq, Jun 2010]

TCP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13032374).

BS2

High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCP1	NM_030752.3 linkuse as main transcript	c.1436A>G	p.Glu479Gly	missense_variant	11/12	ENST00000321394.12
TCP1	NM_001008897.2 linkuse as main transcript	c.971A>G	p.Glu324Gly	missense_variant	10/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCP1	ENST00000321394.12 linkuse as main transcript	c.1436A>G	p.Glu479Gly	missense_variant	11/12	1	NM_030752.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD3 exomes

AF:

0.0000124

AC:

AN:

241838

Hom.:

AF XY:

0.00

AC XY:

AN XY:

130866

show subpopulations

Gnomad AFR exome

AF:

0.000186

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000138

AC:

AN:

1452874

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722716

show subpopulations

Gnomad4 AFR exome

AF:

0.0000306

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:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 23, 2023

The c.1436A>G (p.E479G) alteration is located in exon 11 (coding exon 11) of the TCP1 gene. This alteration results from a A to G substitution at nucleotide position 1436, causing the glutamic acid (E) at amino acid position 479 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

0.11

BayesDel_addAF

Benign

-0.072

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.45

T;.;T

Eigen

Benign

-0.11

Eigen_PC

Benign

0.17

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-2.1

N;D;D

REVEL

Benign

0.21

Sift

Benign

0.092

T;T;T

Sift4G

Benign

0.16

T;T;T

Polyphen

0.0030

B;.;.

Vest4

0.20

MVP

0.25

MPC

0.58

ClinPred

0.33

GERP RS

6.0

Varity_R

0.32

gMVP

0.66

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over