chr6-159778994-A-C

Variant names:

• chr6-159778994-A-C
• rs4832
• NM_030752.3:c.*51T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030752.3(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 NM_030752.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151
• Publications: 23 publications found

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]

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 Gene-Disease associations (from GenCC):

• acetyl-CoA acetyltransferase-2 deficiency

  Inheritance: AR, Unknown Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030752.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCP1	NM_030752.3	MANE Select	c.*51T>G		3_prime_UTR	Exon 12 of 12	NP_110379.2	P17987
	ACAT2	NM_005891.3	MANE Select	c.*165A>C		3_prime_UTR	Exon 9 of 9	NP_005882.2	Q9BWD1-1
	ACAT2	NM_001303253.1		c.*165A>C		3_prime_UTR	Exon 9 of 9	NP_001290182.1	Q9BWD1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCP1	ENST00000321394.12	TSL:1 MANE Select	c.*51T>G		3_prime_UTR	Exon 12 of 12	ENSP00000317334.7	P17987
	ACAT2	ENST00000367048.5	TSL:1 MANE Select	c.*165A>C		3_prime_UTR	Exon 9 of 9	ENSP00000356015.4	Q9BWD1-1
	TCP1	ENST00000934596.1		c.*51T>G		3_prime_UTR	Exon 12 of 12	ENSP00000604655.1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30337 AN: 152106 Hom.: 3187 Cov.: 32

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

GnomAD2 exomes AF: 0.213 AC: 50263 AN: 235820 AF XY: 0.216

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 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.: 28 AF XY: 0.203 AC XY: 144031 AN XY: 709116

African (AFR) AF: 0.178 AC: 5800 AN: 32496

American (AMR) AF: 0.179 AC: 7660 AN: 42774

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 3115 AN: 24952

East Asian (EAS) AF: 0.382 AC: 15025 AN: 39344

South Asian (SAS) AF: 0.267 AC: 22075 AN: 82734

European-Finnish (FIN) AF: 0.243 AC: 12797 AN: 52652

Middle Eastern (MID) AF: 0.212 AC: 1190 AN: 5626

European-Non Finnish (NFE) AF: 0.190 AC: 206862 AN: 1089174

Other (OTH) AF: 0.200 AC: 11802 AN: 59064

GnomAD4 genome AF: 0.199 AC: 30348 AN: 152224 Hom.: 3188 Cov.: 32 AF XY: 0.206 AC XY: 15302 AN XY: 74422

African (AFR) AF: 0.183 AC: 7605 AN: 41542

American (AMR) AF: 0.204 AC: 3120 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 408 AN: 3468

East Asian (EAS) AF: 0.402 AC: 2082 AN: 5176

South Asian (SAS) AF: 0.281 AC: 1356 AN: 4828

European-Finnish (FIN) AF: 0.252 AC: 2672 AN: 10590

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12504 AN: 68014

Other (OTH) AF: 0.209 AC: 442 AN: 2112

Alfa AF: 0.182 Hom.: 3465

Bravo AF: 0.193

Asia WGS AF: 0.300 AC: 1041 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.1
DANN	Benign	0.68
PhyloP100		-0.15
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4832; hg19: chr6-160200026; COSMIC: COSV58458988; COSMIC: COSV58458988;