20-47654639-A-G

Variant names:

• chr20-47654639-A-G
• rs11699879
• NM_181659.3:c.*1222A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181659.3(NCOA3):​c.*1222A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,436 control chromosomes in the GnomAD database, including 4,622 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 0.23 (4614 hom., cov: 32)
  • Exomes 𝑓: 0.18 (8 hom.)
• Consequence: NCOA3 NM_181659.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.488
• Publications: 10 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.292 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOA3	NM_181659.3	MANE Select	c.*1222A>G		3_prime_UTR	Exon 23 of 23	NP_858045.1	Q9Y6Q9-1
	NCOA3	NM_001174087.2		c.*1222A>G		3_prime_UTR	Exon 23 of 23	NP_001167558.1
	NCOA3	NM_006534.4		c.*1222A>G		3_prime_UTR	Exon 23 of 23	NP_006525.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOA3	ENST00000371998.8	TSL:1 MANE Select	c.*1222A>G		3_prime_UTR	Exon 23 of 23	ENSP00000361066.3	Q9Y6Q9-1
	NCOA3	ENST00000372004.7	TSL:1	c.*1222A>G		3_prime_UTR	Exon 23 of 23	ENSP00000361073.1	Q9Y6Q9-5
	NCOA3	ENST00000371997.3	TSL:1	c.*1222A>G		3_prime_UTR	Exon 23 of 23	ENSP00000361065.3	Q9Y6Q9-3

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35577 AN: 151908 Hom.: 4619 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.263

GnomAD4 exome AF: 0.179 AC: 73 AN: 408 Hom.: 8 Cov.: 0 AF XY: 0.165 AC XY: 40 AN XY: 242

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.177 AC: 71 AN: 402

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.234 AC: 35582 AN: 152028 Hom.: 4614 Cov.: 32 AF XY: 0.230 AC XY: 17072 AN XY: 74294

African (AFR) AF: 0.132 AC: 5454 AN: 41460

American (AMR) AF: 0.225 AC: 3442 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1180 AN: 3472

East Asian (EAS) AF: 0.232 AC: 1201 AN: 5170

South Asian (SAS) AF: 0.258 AC: 1245 AN: 4820

European-Finnish (FIN) AF: 0.178 AC: 1884 AN: 10556

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20084 AN: 67972

Other (OTH) AF: 0.264 AC: 557 AN: 2112

Alfa AF: 0.277 Hom.: 7813

Bravo AF: 0.234

Asia WGS AF: 0.232 AC: 812 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.1
DANN	Benign	0.79
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11699879; hg19: chr20-46283383;