Variant rs6094752 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.051 ( 234 hom., cov: 32)

Exomes 𝑓: 0.044 ( 1680 hom. )

Consequence

NCOA3
NM_181659.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.41

Variant links:

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]

NCOA3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NCOA3	NM_181659.3 linkuse as main transcript	c.652C>T	p.Arg218Cys	missense_variant	7/23	ENST00000371998.8
NCOA3	NM_001174087.2 linkuse as main transcript	c.652C>T	p.Arg218Cys	missense_variant	7/23
NCOA3	NM_006534.4 linkuse as main transcript	c.652C>T	p.Arg218Cys	missense_variant	7/23
NCOA3	NM_001174088.2 linkuse as main transcript	c.652C>T	p.Arg218Cys	missense_variant	7/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCOA3	ENST00000371998.8 linkuse as main transcript	c.652C>T	p.Arg218Cys	missense_variant	7/23	1	NM_181659.3	P4	Q9Y6Q9-1
NCOA3	ENST00000372004.7 linkuse as main transcript	c.652C>T	p.Arg218Cys	missense_variant	7/23	1		A2	Q9Y6Q9-5
NCOA3	ENST00000371997.3 linkuse as main transcript	c.652C>T	p.Arg218Cys	missense_variant	7/23	1		A2	Q9Y6Q9-3
NCOA3	ENST00000497292.1 linkuse as main transcript	n.295C>T		non_coding_transcript_exon_variant	2/4	5

Frequencies

GnomAD3 genomes

AF:

0.0514

AC:

7815

AN:

152118

Hom.:

234

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0410

AC:

10311

AN:

251198

Hom.:

247

AF XY:

0.0430

AC XY:

5832

AN XY:

135746

show subpopulations

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 SAS exome

AF:

0.0513

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.:

AF XY:

0.0452

AC XY:

32885

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.0656

Gnomad4 AMR exome

AF:

0.0304

Gnomad4 ASJ exome

AF:

0.0268

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0531

Gnomad4 FIN exome

AF:

0.0341

Gnomad4 NFE exome

AF:

0.0455

Gnomad4 OTH exome

AF:

0.0457

GnomAD4 genome

AF:

0.0513

AC:

7815

AN:

152234

Hom.:

234

Cov.:

AF XY:

0.0503

AC XY:

3745

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0694

Gnomad4 AMR

AF:

0.0487

Gnomad4 ASJ

AF:

0.0297

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0504

Gnomad4 FIN

AF:

0.0351

Gnomad4 NFE

AF:

0.0476

Gnomad4 OTH

AF:

0.0558

Alfa

AF:

0.0488

Hom.:

456

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:

AN:

3478

EpiCase

AF:

0.0530

EpiControl

AF:

0.0525

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.44

.;T;.

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.42

T;T;T

MetaRNN

Benign

0.0030

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

M;M;M

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-3.4

D;D;D

REVEL

Benign

0.20

Sift

Benign

0.18

T;T;T

Sift4G

Uncertain

0.057

T;T;T

Polyphen

0.56

P;B;D

Vest4

0.57

MPC

0.50

ClinPred

0.045

GERP RS

6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.36

gMVP

0.50

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over