Variant rs2230783 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_181659.3(NCOA3):c.2329T>G(p.Ser777Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000457 in 1,613,830 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0025 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 2 hom. )

Consequence

NCOA3
NM_181659.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.51

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00469175).

BS2

High AC in GnomAd4 at 375 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOA3	NM_181659.3 link	c.2329T>G	p.Ser777Ala	missense_variant	12/23	ENST00000371998.8	NP_858045.1	Q9Y6Q9-1
NCOA3	NM_001174087.2 link	c.2329T>G	p.Ser777Ala	missense_variant	12/23		NP_001167558.1	Q59EE8
NCOA3	NM_006534.4 link	c.2329T>G	p.Ser777Ala	missense_variant	12/23		NP_006525.2	Q9Y6Q9-5
NCOA3	NM_001174088.2 link	c.2359T>G	p.Ser787Ala	missense_variant	12/23		NP_001167559.1	Q9Y6Q9-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NCOA3	ENST00000371998.8 link	c.2329T>G	p.Ser777Ala	missense_variant	12/23	1	NM_181659.3	ENSP00000361066.3	Q9Y6Q9-1
NCOA3	ENST00000372004.7 link	c.2329T>G	p.Ser777Ala	missense_variant	12/23	1		ENSP00000361073.1	Q9Y6Q9-5
NCOA3	ENST00000371997.3 link	c.2359T>G	p.Ser787Ala	missense_variant	12/23	1		ENSP00000361065.3	Q9Y6Q9-3

Frequencies

GnomAD3 genomes

AF:

0.00246

AC:

375

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00847

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000691

AC:

172

AN:

248834

Hom.:

AF XY:

0.000542

AC XY:

AN XY:

134676

show subpopulations

Gnomad AFR exome

AF:

0.00880

Gnomad AMR exome

AF:

0.000608

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000449

Gnomad OTH exome

AF:

0.000492

GnomAD4 exome

AF:

0.000248

AC:

362

AN:

1461580

Hom.:

Cov.:

AF XY:

0.000212

AC XY:

154

AN XY:

727040

show subpopulations

Gnomad4 AFR exome

AF:

0.00798

Gnomad4 AMR exome

AF:

0.000694

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000261

Gnomad4 OTH exome

AF:

0.000414

GnomAD4 genome

AF:

0.00246

AC:

375

AN:

152250

Hom.:

Cov.:

AF XY:

0.00242

AC XY:

180

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00845

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000533

Hom.:

Bravo

AF:

0.00276

ESP6500AA

AF:

0.00613

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000857

AC:

104

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.071

.;T;.

Eigen

Benign

0.026

Eigen_PC

Benign

0.20

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.78

T;T;T

MetaRNN

Benign

0.0047

T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.9

L;L;.

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.18

Sift

Benign

0.48

T;T;T

Sift4G

Benign

0.60

T;T;T

Polyphen

0.017

B;B;P

Vest4

0.39

MVP

0.31

MPC

0.43

ClinPred

0.028

GERP RS

5.7

Varity_R

0.095

gMVP

0.099

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