chr1-156344592-A-T

Position:

• chr1-156344592-A-T

Variant summary

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

The ENST00000368254.6(TSACC):​c.47A>T​(p.Glu16Val) 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. 13/21 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)
• Consequence: TSACC ENST00000368254.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.26

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]

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 (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=0.2268984).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSACC	NM_001304817.2	c.47A>T	p.Glu16Val	missense_variant	3/4	ENST00000368254.6	NP_001291746.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSACC	ENST00000368254.6	c.47A>T	p.Glu16Val	missense_variant	3/4	1	NM_001304817.2	ENSP00000357237.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Jan 05, 2022

The c.47A>T (p.E16V) alteration is located in exon 3 (coding exon 2) of the TSACC gene. This alteration results from a A to T substitution at nucleotide position 47, causing the glutamic acid (E) at amino acid position 16 to be replaced by a valine (V). 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	0.26
BayesDel_addAF	Benign	0.0069	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.067	T;T;.;T;.;T;.;T
Eigen	Benign	0.10
Eigen_PC	Benign	0.069
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.68	.;.;.;.;.;.;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.23	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L;L;.;L;.;L;.;L
MutationTaster	Benign	0.85	N;N;N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-7.0	D;D;.;D;.;D;.;D
REVEL	Uncertain	0.31
Sift	Pathogenic	0.0	D;D;.;D;.;D;.;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D;D
Polyphen		0.95	P;P;.;P;.;P;.;P
Vest4		0.37
MutPred		0.18		Loss of ubiquitination at K15 (P = 0.0148);Loss of ubiquitination at K15 (P = 0.0148);Loss of ubiquitination at K15 (P = 0.0148);Loss of ubiquitination at K15 (P = 0.0148);Loss of ubiquitination at K15 (P = 0.0148);Loss of ubiquitination at K15 (P = 0.0148);Loss of ubiquitination at K15 (P = 0.0148);Loss of ubiquitination at K15 (P = 0.0148);
MVP		0.53
MPC		0.48
ClinPred		0.84	D
GERP RS		2.5
Varity_R		0.57
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: chr1-156314383;