6-159786017-T-C

Variant names:

• chr6-159786017-T-C
• rs2273828
• NM_030752.3:c.280-20A>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.280-20A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 1,592,990 control chromosomes in the GnomAD database, including 244,020 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 0.46 (18055 hom., cov: 32)
  • Exomes 𝑓: 0.55 (225965 hom.)
• Consequence: TCP1 NM_030752.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.728
• Publications: 23 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=-0.86).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCP1	NM_030752.3	MANE Select	c.280-20A>G		intron	N/A	NP_110379.2	P17987
	TCP1	NM_001008897.2		c.-186-20A>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.280-20A>G		intron	N/A	ENSP00000317334.7	P17987
	TCP1	ENST00000934596.1		c.280-20A>G		intron	N/A	ENSP00000604655.1
	TCP1	ENST00000934597.1		c.280-20A>G		intron	N/A	ENSP00000604656.1

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69469 AN: 151910 Hom.: 18049 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.463

GnomAD2 exomes AF: 0.522 AC: 129095 AN: 247442 AF XY: 0.524

Gnomad AFR exome AF: 0.209

Gnomad AMR exome AF: 0.639

Gnomad ASJ exome AF: 0.556

Gnomad EAS exome AF: 0.184

Gnomad FIN exome AF: 0.573

Gnomad NFE exome AF: 0.578

Gnomad OTH exome AF: 0.546

GnomAD4 exome AF: 0.553 AC: 797118 AN: 1440962 Hom.: 225965 Cov.: 25 AF XY: 0.551 AC XY: 395441 AN XY: 717832

African (AFR) AF: 0.212 AC: 6977 AN: 32978

American (AMR) AF: 0.631 AC: 28018 AN: 44372

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 14372 AN: 25996

East Asian (EAS) AF: 0.183 AC: 7221 AN: 39520

South Asian (SAS) AF: 0.502 AC: 43029 AN: 85722

European-Finnish (FIN) AF: 0.579 AC: 30471 AN: 52582

Middle Eastern (MID) AF: 0.485 AC: 2773 AN: 5718

European-Non Finnish (NFE) AF: 0.579 AC: 633380 AN: 1094430

Other (OTH) AF: 0.518 AC: 30877 AN: 59644

GnomAD4 genome AF: 0.457 AC: 69468 AN: 152028 Hom.: 18055 Cov.: 32 AF XY: 0.456 AC XY: 33859 AN XY: 74294

African (AFR) AF: 0.218 AC: 9067 AN: 41500

American (AMR) AF: 0.544 AC: 8319 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 1949 AN: 3466

East Asian (EAS) AF: 0.183 AC: 947 AN: 5170

South Asian (SAS) AF: 0.497 AC: 2387 AN: 4804

European-Finnish (FIN) AF: 0.570 AC: 6003 AN: 10528

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.577 AC: 39233 AN: 67966

Other (OTH) AF: 0.458 AC: 966 AN: 2110

Alfa AF: 0.534 Hom.: 12769

Bravo AF: 0.444

Asia WGS AF: 0.352 AC: 1226 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	1.0
DANN	Benign	0.55
PhyloP100		-0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=7/93	disease causing

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: rs2273828; hg19: chr6-160207049; COSMIC: COSV58457939; COSMIC: COSV58457939;