rs2076546

Variant names:

• chr20-47639749-A-G
• rs2076546
• NM_181659.3:c.2880A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_181659.3(NCOA3):​c.2880A>G​(p.Thr960Thr) 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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NCOA3	NM_181659.3	c.2880A>G	p.Thr960Thr	synonymous_variant	Exon 15 of 23	ENST00000371998.8	NP_858045.1
NCOA3	NM_001174087.2	c.2880A>G	p.Thr960Thr	synonymous_variant	Exon 15 of 23		NP_001167558.1
NCOA3	NM_006534.4	c.2880A>G	p.Thr960Thr	synonymous_variant	Exon 15 of 23		NP_006525.2
NCOA3	NM_001174088.2	c.2865A>G	p.Thr955Thr	synonymous_variant	Exon 15 of 23		NP_001167559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOA3	ENST00000371998.8	c.2880A>G	p.Thr960Thr	synonymous_variant	Exon 15 of 23	1	NM_181659.3	ENSP00000361066.3
NCOA3	ENST00000372004.7	c.2880A>G	p.Thr960Thr	synonymous_variant	Exon 15 of 23	1		ENSP00000361073.1
NCOA3	ENST00000371997.3	c.2865A>G	p.Thr955Thr	synonymous_variant	Exon 15 of 23	1		ENSP00000361065.3

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

GnomAD2 exomes AF: 0.0925 AC: 23247 AN: 251344 AF XY: 0.0921

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 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 AC: 8200 AN: 33480

Gnomad4 AMR exome AF: 0.0618 AC: 2762 AN: 44724

Gnomad4 ASJ exome AF: 0.119 AC: 3111 AN: 26136

Gnomad4 EAS exome AF: 0.104 AC: 4124 AN: 39698

Gnomad4 SAS exome AF: 0.108 AC: 9327 AN: 86258

Gnomad4 FIN exome AF: 0.0529 AC: 2824 AN: 53418

Gnomad4 NFE exome AF: 0.0794 AC: 88301 AN: 1111990

Gnomad4 Remaining exome AF: 0.0989 AC: 5975 AN: 60396

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 AC: 0.238847 AN: 0.238847

Gnomad4 AMR AF: 0.0860 AC: 0.0860377 AN: 0.0860377

Gnomad4 ASJ AF: 0.123 AC: 0.123272 AN: 0.123272

Gnomad4 EAS AF: 0.0836 AC: 0.0835585 AN: 0.0835585

Gnomad4 SAS AF: 0.114 AC: 0.113806 AN: 0.113806

Gnomad4 FIN AF: 0.0516 AC: 0.051594 AN: 0.051594

Gnomad4 NFE AF: 0.0852 AC: 0.0852425 AN: 0.0852425

Gnomad4 OTH AF: 0.134 AC: 0.133743 AN: 0.133743

Alfa AF: 0.106 Hom.: 3149

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
Mutation Taster		=100/0	polymorphism (auto)

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;