rs2076546

Positions:

• chr20-47639749-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_181659.3(NCOA3):​c.2880A>G​(p.Thr960=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0898 in 1,614,030 control chromosomes in the GnomAD database, including 7,859 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 0.13 (1711 hom., cov: 32)
  • Exomes 𝑓: 0.086 (6148 hom.)
• Consequence: NCOA3 NM_181659.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.947

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=-0.947 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCOA3	NM_181659.3	c.2880A>G	p.Thr960=	synonymous_variant	15/23	ENST00000371998.8
NCOA3	NM_001174087.2	c.2880A>G	p.Thr960=	synonymous_variant	15/23
NCOA3	NM_006534.4	c.2880A>G	p.Thr960=	synonymous_variant	15/23
NCOA3	NM_001174088.2	c.2865A>G	p.Thr955=	synonymous_variant	15/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCOA3	ENST00000371998.8	c.2880A>G	p.Thr960=	synonymous_variant	15/23	1	NM_181659.3	P4
NCOA3	ENST00000372004.7	c.2880A>G	p.Thr960=	synonymous_variant	15/23	1		A2
NCOA3	ENST00000371997.3	c.2865A>G	p.Thr955=	synonymous_variant	15/23	1		A2

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19404 AN: 152044 Hom.: 1706 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.0863

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.0838

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0516

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.0852

Gnomad OTH AF: 0.135

GnomAD3 exomes AF: 0.0925 AC: 23247 AN: 251344 Hom.: 1306 AF XY: 0.0921 AC XY: 12509 AN XY: 135884

Gnomad AFR exome AF: 0.241

Gnomad AMR exome AF: 0.0569

Gnomad ASJ exome AF: 0.113

Gnomad EAS exome AF: 0.0779

Gnomad SAS exome AF: 0.108

Gnomad FIN exome AF: 0.0526

Gnomad NFE exome AF: 0.0858

Gnomad OTH exome AF: 0.0982

GnomAD4 exome AF: 0.0859 AC: 125583 AN: 1461868 Hom.: 6148 Cov.: 33 AF XY: 0.0871 AC XY: 63323 AN XY: 727234

Gnomad4 AFR exome AF: 0.245

Gnomad4 AMR exome AF: 0.0618

Gnomad4 ASJ exome AF: 0.119

Gnomad4 EAS exome AF: 0.104

Gnomad4 SAS exome AF: 0.108

Gnomad4 FIN exome AF: 0.0529

Gnomad4 NFE exome AF: 0.0794

Gnomad4 OTH exome AF: 0.0989

GnomAD4 genome AF: 0.128 AC: 19421 AN: 152162 Hom.: 1711 Cov.: 32 AF XY: 0.125 AC XY: 9290 AN XY: 74400

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.0860

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.0836

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0516

Gnomad4 NFE AF: 0.0852

Gnomad4 OTH AF: 0.134

Alfa AF: 0.0980 Hom.: 1650

Bravo AF: 0.133

Asia WGS AF: 0.122 AC: 425 AN: 3478

EpiCase AF: 0.0918

EpiControl AF: 0.0931

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.1
DANN	Benign	0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2076546; hg19: chr20-46268493;