NM_030752.3:c.*390A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_030752.3(TCP1):​c.*390A>T variant causes a 3 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

TCP1
NM_030752.3 3_prime_UTR

Scores

2
Splicing: ADA: 0.00007916
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.209

Publications

29 publications found
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]
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

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.69).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TCP1NM_030752.3 linkc.*390A>T 3_prime_UTR_variant Exon 12 of 12 ENST00000321394.12 NP_110379.2 P17987
ACAT2NM_005891.3 linkc.1024-4T>A splice_region_variant, intron_variant Intron 8 of 8 ENST00000367048.5 NP_005882.2 Q9BWD1-1
TCP1NM_001008897.2 linkc.*390A>T 3_prime_UTR_variant Exon 11 of 11 NP_001008897.1 E7EQR6
ACAT2NM_001303253.1 linkc.1111-4T>A splice_region_variant, intron_variant Intron 8 of 8 NP_001290182.1 Q9BWD1-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TCP1ENST00000321394.12 linkc.*390A>T 3_prime_UTR_variant Exon 12 of 12 1 NM_030752.3 ENSP00000317334.7 P17987
ACAT2ENST00000367048.5 linkc.1024-4T>A splice_region_variant, intron_variant Intron 8 of 8 1 NM_005891.3 ENSP00000356015.4 Q9BWD1-1
ACAT2ENST00000472052.1 linkn.1254-4T>A splice_region_variant, intron_variant Intron 3 of 3 2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1461288
Hom.:
0
Cov.:
41
AF XY:
0.00
AC XY:
0
AN XY:
726908
African (AFR)
AF:
0.00
AC:
0
AN:
33464
American (AMR)
AF:
0.00
AC:
0
AN:
44698
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26110
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39676
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86204
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53412
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111590
Other (OTH)
AF:
0.00
AC:
0
AN:
60366
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.00
Hom.:
77664

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.69
CADD
Benign
6.7
DANN
Benign
0.85
PhyloP100
0.21

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000079
dbscSNV1_RF
Benign
0.0040
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

Other links and lift over

dbSNP: rs15982; hg19: chr6-160199687; API