20-47627680-C-T

Variant names:

• chr20-47627680-C-T
• rs6094752
• NM_181659.3:c.652C>T

Variant summary

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

The NM_181659.3(NCOA3):​c.652C>T​(p.Arg218Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0449 in 1,613,884 control chromosomes in the GnomAD database, including 1,914 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 0.051 (234 hom., cov: 32)
  • Exomes 𝑓: 0.044 (1680 hom.)
• Consequence: NCOA3 NM_181659.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.41
• Publications: 26 publications found

Genes affected

NCOA3 (HGNC:7670): (nuclear receptor coactivator 3) The protein encoded by this gene is a nuclear receptor coactivator that interacts with nuclear hormone receptors to enhance their transcriptional activator functions. The encoded protein has histone acetyltransferase activity and recruits p300/CBP-associated factor and CREB binding protein as part of a multisubunit coactivation complex. This protein is initially found in the cytoplasm but is translocated into the nucleus upon phosphorylation. Several transcript variants encoding different isoforms have been found for this gene. In addition, a polymorphic repeat region is found in the C-terminus of the encoded protein. [provided by RefSeq, Mar 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0030201674).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0673 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181659.3. 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
	NCOA3	NM_181659.3	MANE Select	c.652C>T	p.Arg218Cys	missense	Exon 7 of 23	NP_858045.1
	NCOA3	NM_001174087.2		c.652C>T	p.Arg218Cys	missense	Exon 7 of 23	NP_001167558.1
	NCOA3	NM_006534.4		c.652C>T	p.Arg218Cys	missense	Exon 7 of 23	NP_006525.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOA3	ENST00000371998.8	TSL:1 MANE Select	c.652C>T	p.Arg218Cys	missense	Exon 7 of 23	ENSP00000361066.3
	NCOA3	ENST00000372004.7	TSL:1	c.652C>T	p.Arg218Cys	missense	Exon 7 of 23	ENSP00000361073.1
	NCOA3	ENST00000371997.3	TSL:1	c.652C>T	p.Arg218Cys	missense	Exon 7 of 23	ENSP00000361065.3

Frequencies

GnomAD3 genomes AF: 0.0514 AC: 7815 AN: 152118 Hom.: 234 Cov.: 32

Gnomad AFR AF: 0.0696

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.0488

Gnomad ASJ AF: 0.0297

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0495

Gnomad FIN AF: 0.0351

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0477

Gnomad OTH AF: 0.0564

GnomAD2 exomes AF: 0.0410 AC: 10311 AN: 251198 AF XY: 0.0430

Gnomad AFR exome AF: 0.0681

Gnomad AMR exome AF: 0.0297

Gnomad ASJ exome AF: 0.0287

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0341

Gnomad NFE exome AF: 0.0464

Gnomad OTH exome AF: 0.0503

GnomAD4 exome AF: 0.0442 AC: 64585 AN: 1461650 Hom.: 1680 Cov.: 32 AF XY: 0.0452 AC XY: 32885 AN XY: 727134

African (AFR) AF: 0.0656 AC: 2197 AN: 33468

American (AMR) AF: 0.0304 AC: 1360 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.0268 AC: 699 AN: 26126

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39688

South Asian (SAS) AF: 0.0531 AC: 4577 AN: 86232

European-Finnish (FIN) AF: 0.0341 AC: 1820 AN: 53416

Middle Eastern (MID) AF: 0.0983 AC: 567 AN: 5766

European-Non Finnish (NFE) AF: 0.0455 AC: 50606 AN: 1111856

Other (OTH) AF: 0.0457 AC: 2758 AN: 60390

GnomAD4 genome AF: 0.0513 AC: 7815 AN: 152234 Hom.: 234 Cov.: 32 AF XY: 0.0503 AC XY: 3745 AN XY: 74442

African (AFR) AF: 0.0694 AC: 2884 AN: 41540

American (AMR) AF: 0.0487 AC: 745 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0297 AC: 103 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5188

South Asian (SAS) AF: 0.0504 AC: 242 AN: 4806

European-Finnish (FIN) AF: 0.0351 AC: 372 AN: 10598

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0476 AC: 3241 AN: 68022

Other (OTH) AF: 0.0558 AC: 118 AN: 2114

Alfa AF: 0.0482 Hom.: 879

Bravo AF: 0.0529

TwinsUK AF: 0.0458 AC: 170

ALSPAC AF: 0.0446 AC: 172

ESP6500AA AF: 0.0658 AC: 290

ESP6500EA AF: 0.0472 AC: 406

ExAC AF: 0.0423 AC: 5142

Asia WGS AF: 0.0230 AC: 80 AN: 3478

EpiCase AF: 0.0530

EpiControl AF: 0.0525

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.44	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.42	T
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		4.4
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.20
Sift	Benign	0.18	T
Sift4G	Uncertain	0.057	T
Polyphen		0.56	P
Vest4		0.57
MPC		0.50
ClinPred		0.045	T
GERP RS		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.36
gMVP		0.50
Mutation Taster		=88/12	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: rs6094752; hg19: chr20-46256424; COSMIC: COSV59066261; COSMIC: COSV59066261;