20-47581409-C-T

Variant names:

• chr20-47581409-C-T
• rs6066394
• NM_181659.3:c.-98-1774C>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.-98-1774C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 151,980 control chromosomes in the GnomAD database, including 7,151 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 0.29 (7151 hom., cov: 32)
• Consequence: NCOA3 NM_181659.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184
• Publications: 6 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 (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.567 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.-98-1774C>T		intron	N/A	NP_858045.1
	NCOA3	NM_001174087.2		c.-98-1774C>T		intron	N/A	NP_001167558.1
	NCOA3	NM_006534.4		c.-98-1774C>T		intron	N/A	NP_006525.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOA3	ENST00000371998.8	TSL:1 MANE Select	c.-98-1774C>T		intron	N/A	ENSP00000361066.3
	NCOA3	ENST00000372004.7	TSL:1	c.-98-1774C>T		intron	N/A	ENSP00000361073.1
	NCOA3	ENST00000371997.3	TSL:1	c.-98-1774C>T		intron	N/A	ENSP00000361065.3

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44397 AN: 151862 Hom.: 7144 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.256

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.292 AC: 44423 AN: 151980 Hom.: 7151 Cov.: 32 AF XY: 0.303 AC XY: 22514 AN XY: 74258

African (AFR) AF: 0.244 AC: 10132 AN: 41468

American (AMR) AF: 0.397 AC: 6053 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 627 AN: 3468

East Asian (EAS) AF: 0.584 AC: 3024 AN: 5174

South Asian (SAS) AF: 0.431 AC: 2067 AN: 4798

European-Finnish (FIN) AF: 0.386 AC: 4068 AN: 10540

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.261 AC: 17718 AN: 67964

Other (OTH) AF: 0.257 AC: 543 AN: 2110

Alfa AF: 0.271 Hom.: 4509

Bravo AF: 0.293

Asia WGS AF: 0.468 AC: 1623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.97
DANN	Benign	0.46
PhyloP100		-0.18
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

Other links and lift over

dbSNP: rs6066394; hg19: chr20-46210153;