NM_030752.3:c.798-140G>C

Variant names:

• chr6-159781250-C-G
• rs2295898
• NM_030752.3:c.798-140G>C

Variant summary

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

The NM_030752.3(TCP1):​c.798-140G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 782,000 control chromosomes in the GnomAD database, including 10,242 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 0.14 (1818 hom., cov: 33)
  • Exomes 𝑓: 0.15 (8424 hom.)
• Consequence: TCP1 NM_030752.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.262
• 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):

• intellectual developmental disorder with polymicrogyria and seizures

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, PanelApp Australia
• neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.383 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.798-140G>C		intron	N/A	NP_110379.2	P17987
	TCP1	NM_001008897.2		c.333-140G>C		intron	N/A	NP_001008897.1	E7EQR6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCP1	ENST00000321394.12	TSL:1 MANE Select	c.798-140G>C		intron	N/A	ENSP00000317334.7	P17987
	TCP1	ENST00000934596.1		c.798-140G>C		intron	N/A	ENSP00000604655.1
	TCP1	ENST00000934597.1		c.798-140G>C		intron	N/A	ENSP00000604656.1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21132 AN: 152020 Hom.: 1818 Cov.: 33

Gnomad AFR AF: 0.0660

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.0928

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.158

GnomAD4 exome AF: 0.150 AC: 94362 AN: 629860 Hom.: 8424 AF XY: 0.151 AC XY: 47977 AN XY: 317090

African (AFR) AF: 0.0550 AC: 724 AN: 13172

American (AMR) AF: 0.160 AC: 1753 AN: 10974

Ashkenazi Jewish (ASJ) AF: 0.0952 AC: 1260 AN: 13232

East Asian (EAS) AF: 0.370 AC: 9557 AN: 25798

South Asian (SAS) AF: 0.200 AC: 6133 AN: 30662

European-Finnish (FIN) AF: 0.204 AC: 6030 AN: 29524

Middle Eastern (MID) AF: 0.167 AC: 402 AN: 2406

European-Non Finnish (NFE) AF: 0.135 AC: 63976 AN: 473868

Other (OTH) AF: 0.150 AC: 4527 AN: 30224

GnomAD4 genome AF: 0.139 AC: 21132 AN: 152140 Hom.: 1818 Cov.: 33 AF XY: 0.146 AC XY: 10886 AN XY: 74374

African (AFR) AF: 0.0659 AC: 2733 AN: 41500

American (AMR) AF: 0.165 AC: 2527 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0928 AC: 322 AN: 3470

East Asian (EAS) AF: 0.397 AC: 2054 AN: 5174

South Asian (SAS) AF: 0.231 AC: 1115 AN: 4828

European-Finnish (FIN) AF: 0.224 AC: 2366 AN: 10564

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9629 AN: 67992

Other (OTH) AF: 0.158 AC: 333 AN: 2114

Alfa AF: 0.136 Hom.: 189

Bravo AF: 0.131

Asia WGS AF: 0.271 AC: 939 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.8
DANN	Benign	0.78
PhyloP100		-0.26
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: rs2295898; hg19: chr6-160202282; COSMIC: COSV58458956; COSMIC: COSV58458956;