chr6-159785083-A-C

Variant names:

• chr6-159785083-A-C
• rs1547094
• NM_030752.3:c.489-236T>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.489-236T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 609,758 control chromosomes in the GnomAD database, including 14,924 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 0.22 (3811 hom., cov: 33)
  • Exomes 𝑓: 0.21 (11113 hom.)
• Consequence: TCP1 NM_030752.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.812
• Publications: 4 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=-0.84).
• 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.489-236T>G		intron	N/A	NP_110379.2	P17987
	TCP1	NM_001008897.2		c.24-236T>G		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.489-236T>G		intron	N/A	ENSP00000317334.7	P17987
	TCP1	ENST00000934596.1		c.489-236T>G		intron	N/A	ENSP00000604655.1
	TCP1	ENST00000934597.1		c.489-236T>G		intron	N/A	ENSP00000604656.1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33294 AN: 152066 Hom.: 3808 Cov.: 33

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.227

GnomAD4 exome AF: 0.212 AC: 96814 AN: 457576 Hom.: 11113 Cov.: 4 AF XY: 0.214 AC XY: 52091 AN XY: 243098

African (AFR) AF: 0.241 AC: 3030 AN: 12588

American (AMR) AF: 0.195 AC: 3459 AN: 17776

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 1759 AN: 13930

East Asian (EAS) AF: 0.378 AC: 11736 AN: 31032

South Asian (SAS) AF: 0.269 AC: 12104 AN: 44976

European-Finnish (FIN) AF: 0.240 AC: 7031 AN: 29296

Middle Eastern (MID) AF: 0.210 AC: 548 AN: 2608

European-Non Finnish (NFE) AF: 0.185 AC: 51720 AN: 279008

Other (OTH) AF: 0.206 AC: 5427 AN: 26362

GnomAD4 genome AF: 0.219 AC: 33318 AN: 152182 Hom.: 3811 Cov.: 33 AF XY: 0.225 AC XY: 16757 AN XY: 74394

African (AFR) AF: 0.252 AC: 10467 AN: 41522

American (AMR) AF: 0.211 AC: 3235 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 409 AN: 3470

East Asian (EAS) AF: 0.402 AC: 2077 AN: 5166

South Asian (SAS) AF: 0.281 AC: 1355 AN: 4820

European-Finnish (FIN) AF: 0.251 AC: 2654 AN: 10576

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12483 AN: 68012

Other (OTH) AF: 0.226 AC: 476 AN: 2110

Alfa AF: 0.199 Hom.: 399

Bravo AF: 0.216

Asia WGS AF: 0.305 AC: 1058 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.6
DANN	Benign	0.67
PhyloP100		0.81
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1547094; hg19: chr6-160206115;