Variant 1-156344589-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000368254.6(TSACC):c.44A>C(p.Lys15Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,586 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: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

TSACC
ENST00000368254.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.702

Variant links:

Genes affected

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:

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:

CCT3 (HGNC:):

CCT3 links:

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ACMG classification

Classification made for transcript

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=0.12565333).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSACC	NM_001304817.2 linkuse as main transcript	c.44A>C	p.Lys15Thr	missense_variant	3/4	ENST00000368254.6	NP_001291746.1	Q96A04

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSACC	ENST00000368254.6 linkuse as main transcript	c.44A>C	p.Lys15Thr	missense_variant	3/4	1	NM_001304817.2	ENSP00000357237.1		Q96A04

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250946

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135636

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1461586

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727106

show subpopulations

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:

0.00000450

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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

Jan 10, 2022

The c.44A>C (p.K15T) alteration is located in exon 3 (coding exon 2) of the TSACC gene. This alteration results from a A to C substitution at nucleotide position 44, causing the lysine (K) at amino acid position 15 to be replaced by a threonine (T). 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

0.12

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.055

T;T;.;T;.;T;.;T

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.57

.;.;.;.;.;.;T;T

M_CAP

Benign

0.0051

MetaRNN

Benign

0.13

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.97

L;L;.;L;.;L;.;L

MutationTaster

Benign

0.78

N;N;N;N;N

PrimateAI

Benign

0.44

PROVEAN

Pathogenic

-4.8

D;D;.;D;.;D;.;D

REVEL

Benign

0.077

Sift

Uncertain

0.0060

D;D;.;D;.;D;.;D

Sift4G

Uncertain

0.022

D;D;D;D;D;D;D;D

Polyphen

0.017

B;B;.;B;.;B;.;B

Vest4

0.30

MutPred

0.12

Loss of ubiquitination at K15 (P = 0.0023);Loss of ubiquitination at K15 (P = 0.0023);Loss of ubiquitination at K15 (P = 0.0023);Loss of ubiquitination at K15 (P = 0.0023);Loss of ubiquitination at K15 (P = 0.0023);Loss of ubiquitination at K15 (P = 0.0023);Loss of ubiquitination at K15 (P = 0.0023);Loss of ubiquitination at K15 (P = 0.0023);

MVP

0.23

MPC

0.48

ClinPred

0.83

GERP RS

2.5

Varity_R

0.23

gMVP

0.19

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