NM_030752.3:c.489-112G>T

Variant names:

• chr6-159784959-C-A
• rs1547093
• NM_030752.3:c.489-112G>T

Variant summary

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

The NM_030752.3(TCP1):​c.489-112G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 1,030,764 control chromosomes in the GnomAD database, including 323,952 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 0.78 (46361 hom., cov: 32)
  • Exomes 𝑓: 0.79 (277591 hom.)
• Consequence: TCP1 NM_030752.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570
• Publications: 8 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]

TCP1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
• intellectual developmental disorder with polymicrogyria and seizures

  Inheritance: AD Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCP1	NM_030752.3	c.489-112G>T		intron_variant	Intron 5 of 11	ENST00000321394.12	NP_110379.2
TCP1	NM_001008897.2	c.24-112G>T		intron_variant	Intron 4 of 10		NP_001008897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCP1	ENST00000321394.12	c.489-112G>T		intron_variant	Intron 5 of 11	1	NM_030752.3	ENSP00000317334.7

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118330 AN: 152056 Hom.: 46333 Cov.: 32

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.837

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.843

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.792

Gnomad OTH AF: 0.792

GnomAD4 exome AF: 0.792 AC: 696204 AN: 878588 Hom.: 277591 Cov.: 11 AF XY: 0.795 AC XY: 364706 AN XY: 458990

African (AFR) AF: 0.729 AC: 14803 AN: 20294

American (AMR) AF: 0.862 AC: 28436 AN: 32986

Ashkenazi Jewish (ASJ) AF: 0.739 AC: 16006 AN: 21652

East Asian (EAS) AF: 0.563 AC: 20117 AN: 35742

South Asian (SAS) AF: 0.848 AC: 58482 AN: 68942

European-Finnish (FIN) AF: 0.842 AC: 39047 AN: 46362

Middle Eastern (MID) AF: 0.837 AC: 3887 AN: 4642

European-Non Finnish (NFE) AF: 0.796 AC: 483404 AN: 606972

Other (OTH) AF: 0.781 AC: 32022 AN: 40996

GnomAD4 genome AF: 0.778 AC: 118410 AN: 152176 Hom.: 46361 Cov.: 32 AF XY: 0.781 AC XY: 58141 AN XY: 74406

African (AFR) AF: 0.738 AC: 30614 AN: 41504

American (AMR) AF: 0.837 AC: 12811 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.747 AC: 2593 AN: 3470

East Asian (EAS) AF: 0.587 AC: 3032 AN: 5164

South Asian (SAS) AF: 0.851 AC: 4106 AN: 4824

European-Finnish (FIN) AF: 0.843 AC: 8933 AN: 10594

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.792 AC: 53859 AN: 68002

Other (OTH) AF: 0.784 AC: 1656 AN: 2112

Alfa AF: 0.783 Hom.: 11887

Bravo AF: 0.773

Asia WGS AF: 0.705 AC: 2451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.4
DANN	Benign	0.41
PhyloP100		0.057
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: rs1547093; hg19: chr6-160205991;