chr6-159781135-G-A

Variant names:

• chr6-159781135-G-A
• rs2295899
• NM_030752.3:c.798-25C>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.798-25C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 1,536,860 control chromosomes in the GnomAD database, including 237,041 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 0.48 (19073 hom., cov: 33)
  • Exomes 𝑓: 0.56 (217968 hom.)
• Consequence: TCP1 NM_030752.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 14 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.572 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCP1	NM_030752.3	MANE Select	c.798-25C>T		intron	N/A	NP_110379.2
	TCP1	NM_001008897.2		c.333-25C>T		intron	N/A	NP_001008897.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCP1	ENST00000321394.12	TSL:1 MANE Select	c.798-25C>T		intron	N/A	ENSP00000317334.7
	TCP1	ENST00000420894.6	TSL:5	c.798-25C>T		intron	N/A	ENSP00000390159.2
	TCP1	ENST00000392168.6	TSL:5	c.333-25C>T		intron	N/A	ENSP00000376008.2

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73283 AN: 151998 Hom.: 19064 Cov.: 33

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.480

GnomAD2 exomes AF: 0.533 AC: 104567 AN: 196162 AF XY: 0.535

Gnomad AFR exome AF: 0.306

Gnomad AMR exome AF: 0.652

Gnomad ASJ exome AF: 0.561

Gnomad EAS exome AF: 0.192

Gnomad FIN exome AF: 0.576

Gnomad NFE exome AF: 0.582

Gnomad OTH exome AF: 0.564

GnomAD4 exome AF: 0.556 AC: 769685 AN: 1384744 Hom.: 217968 Cov.: 26 AF XY: 0.554 AC XY: 379707 AN XY: 685894

African (AFR) AF: 0.306 AC: 9002 AN: 29444

American (AMR) AF: 0.636 AC: 18981 AN: 29854

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 12618 AN: 22768

East Asian (EAS) AF: 0.184 AC: 6835 AN: 37074

South Asian (SAS) AF: 0.507 AC: 37907 AN: 74816

European-Finnish (FIN) AF: 0.581 AC: 30015 AN: 51656

Middle Eastern (MID) AF: 0.488 AC: 2659 AN: 5448

European-Non Finnish (NFE) AF: 0.578 AC: 621830 AN: 1076734

Other (OTH) AF: 0.524 AC: 29838 AN: 56950

GnomAD4 genome AF: 0.482 AC: 73298 AN: 152116 Hom.: 19073 Cov.: 33 AF XY: 0.480 AC XY: 35691 AN XY: 74374

African (AFR) AF: 0.305 AC: 12669 AN: 41474

American (AMR) AF: 0.555 AC: 8481 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 1951 AN: 3472

East Asian (EAS) AF: 0.183 AC: 946 AN: 5174

South Asian (SAS) AF: 0.496 AC: 2398 AN: 4830

European-Finnish (FIN) AF: 0.571 AC: 6030 AN: 10560

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.577 AC: 39223 AN: 67998

Other (OTH) AF: 0.475 AC: 1004 AN: 2112

Alfa AF: 0.534 Hom.: 7897

Bravo AF: 0.472

Asia WGS AF: 0.359 AC: 1247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.53
DANN	Benign	0.28
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2295899; hg19: chr6-160202167; COSMIC: COSV58457922; COSMIC: COSV58457922;