Variant chr6-159778994-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000321394.12(TCP1):c.*51T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,581,040 control chromosomes in the GnomAD database, including 33,207 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.20 ( 3188 hom., cov: 32)

Exomes 𝑓: 0.20 ( 30019 hom. )

Consequence

TCP1
ENST00000321394.12 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.151

Variant links:

Genes affected

ACAT2 (HGNC:94): (acetyl-CoA acetyltransferase 2) The product of this gene is an enzyme involved in lipid metabolism, and it encodes cytosolic acetoacetyl-CoA thiolase. This gene shows complementary overlapping with the 3-prime region of the TCP1 gene in both mouse and human. These genes are encoded on opposite strands of DNA, as well as in opposite transcriptional orientation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2014]

ACAT2 links:

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
ACAT2	NM_005891.3 linkuse as main transcript	c.*165A>C	3_prime_UTR_variant	9/9	ENST00000367048.5	NP_005882.2
TCP1	NM_030752.3 linkuse as main transcript	c.*51T>G	3_prime_UTR_variant	12/12	ENST00000321394.12	NP_110379.2
TCP1	NM_001008897.2 linkuse as main transcript	c.*51T>G	3_prime_UTR_variant	11/11		NP_001008897.1
ACAT2	NM_001303253.1 linkuse as main transcript	c.*165A>C	3_prime_UTR_variant	9/9		NP_001290182.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCP1	ENST00000321394.12 linkuse as main transcript	c.*51T>G		3_prime_UTR_variant	12/12	1	NM_030752.3	ENSP00000317334	P1
ACAT2	ENST00000367048.5 linkuse as main transcript	c.*165A>C		3_prime_UTR_variant	9/9	1	NM_005891.3	ENSP00000356015	P1	Q9BWD1-1

Frequencies

GnomAD3 genomes

AF:

0.199

AC:

30337

AN:

152106

Hom.:

3187

Cov.:

show subpopulations

Gnomad AFR

AF:

0.183

Gnomad AMI

AF:

0.124

Gnomad AMR

AF:

0.204

Gnomad ASJ

AF:

0.118

Gnomad EAS

AF:

0.402

Gnomad SAS

AF:

0.280

Gnomad FIN

AF:

0.252

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.184

Gnomad OTH

AF:

0.210

GnomAD3 exomes

AF:

0.213

AC:

50263

AN:

235820

Hom.:

5933

AF XY:

0.216

AC XY:

27565

AN XY:

127678

show subpopulations

Gnomad AFR exome

AF:

0.180

Gnomad AMR exome

AF:

0.176

Gnomad ASJ exome

AF:

0.124

Gnomad EAS exome

AF:

0.396

Gnomad SAS exome

AF:

0.268

Gnomad FIN exome

AF:

0.249

Gnomad NFE exome

AF:

0.186

Gnomad OTH exome

AF:

0.203

GnomAD4 exome

AF:

0.200

AC:

286326

AN:

1428816

Hom.:

30019

Cov.:

AF XY:

0.203

AC XY:

144031

AN XY:

709116

show subpopulations

Gnomad4 AFR exome

AF:

0.178

Gnomad4 AMR exome

AF:

0.179

Gnomad4 ASJ exome

AF:

0.125

Gnomad4 EAS exome

AF:

0.382

Gnomad4 SAS exome

AF:

0.267

Gnomad4 FIN exome

AF:

0.243

Gnomad4 NFE exome

AF:

0.190

Gnomad4 OTH exome

AF:

0.200

GnomAD4 genome

AF:

0.199

AC:

30348

AN:

152224

Hom.:

3188

Cov.:

AF XY:

0.206

AC XY:

15302

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.183

Gnomad4 AMR

AF:

0.204

Gnomad4 ASJ

AF:

0.118

Gnomad4 EAS

AF:

0.402

Gnomad4 SAS

AF:

0.281

Gnomad4 FIN

AF:

0.252

Gnomad4 NFE

AF:

0.184

Gnomad4 OTH

AF:

0.209

Alfa

AF:

0.181

Hom.:

2673

Bravo

AF:

0.193

Asia WGS

AF:

0.300

AC:

1041

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

7.1

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over