chr6-159785684-T-C

Variant names:

• chr6-159785684-T-C
• rs3818298
• NM_030752.3:c.378-188A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_030752.3(TCP1):​c.378-188A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 791,580 control chromosomes in the GnomAD database, including 17,942 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 0.20 (3170 hom., cov: 33)
  • Exomes 𝑓: 0.21 (14772 hom.)
• Consequence: TCP1 NM_030752.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.80
• Publications: 15 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]

SNORA29 (HGNC:32619): (small nucleolar RNA, H/ACA box 29)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• 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.378-188A>G		intron	N/A	NP_110379.2	P17987
	TCP1	NM_001008897.2		c.-88-188A>G		intron	N/A	NP_001008897.1	E7EQR6
	SNORA29	NR_002965.1		n.50A>G		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCP1	ENST00000321394.12	TSL:1 MANE Select	c.378-188A>G		intron	N/A	ENSP00000317334.7	P17987
	TCP1	ENST00000934596.1		c.378-188A>G		intron	N/A	ENSP00000604655.1
	TCP1	ENST00000934597.1		c.378-188A>G		intron	N/A	ENSP00000604656.1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30206 AN: 151978 Hom.: 3169 Cov.: 33

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.210

GnomAD2 exomes AF: 0.210 AC: 49131 AN: 233618 AF XY: 0.214

Gnomad AFR exome AF: 0.177

Gnomad AMR exome AF: 0.174

Gnomad ASJ exome AF: 0.121

Gnomad EAS exome AF: 0.394

Gnomad FIN exome AF: 0.247

Gnomad NFE exome AF: 0.185

Gnomad OTH exome AF: 0.200

GnomAD4 exome AF: 0.207 AC: 132349 AN: 639484 Hom.: 14772 Cov.: 7 AF XY: 0.210 AC XY: 73104 AN XY: 347824

African (AFR) AF: 0.176 AC: 3185 AN: 18090

American (AMR) AF: 0.179 AC: 7762 AN: 43482

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 2633 AN: 21082

East Asian (EAS) AF: 0.380 AC: 13708 AN: 36110

South Asian (SAS) AF: 0.267 AC: 18394 AN: 68890

European-Finnish (FIN) AF: 0.241 AC: 9189 AN: 38164

Middle Eastern (MID) AF: 0.208 AC: 873 AN: 4188

European-Non Finnish (NFE) AF: 0.186 AC: 69900 AN: 375596

Other (OTH) AF: 0.198 AC: 6705 AN: 33882

GnomAD4 genome AF: 0.199 AC: 30217 AN: 152096 Hom.: 3170 Cov.: 33 AF XY: 0.205 AC XY: 15235 AN XY: 74346

African (AFR) AF: 0.181 AC: 7525 AN: 41504

American (AMR) AF: 0.204 AC: 3120 AN: 15276

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

East Asian (EAS) AF: 0.403 AC: 2084 AN: 5176

South Asian (SAS) AF: 0.281 AC: 1354 AN: 4824

European-Finnish (FIN) AF: 0.253 AC: 2668 AN: 10548

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12455 AN: 67978

Other (OTH) AF: 0.210 AC: 443 AN: 2114

Alfa AF: 0.183 Hom.: 1437

Bravo AF: 0.192

Asia WGS AF: 0.300 AC: 1040 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	16
DANN	Benign	0.91
PhyloP100		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3818298; hg19: chr6-160206716; COSMIC: COSV58458998; COSMIC: COSV58458998;