20-47654639-A-G

Position:

• chr20-47654639-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOA3	NM_181659.3	c.*1222A>G		3_prime_UTR_variant	23/23	ENST00000371998.8	NP_858045.1
NCOA3	NM_001174087.2	c.*1222A>G		3_prime_UTR_variant	23/23		NP_001167558.1
NCOA3	NM_001174088.2	c.*1222A>G		3_prime_UTR_variant	23/23		NP_001167559.1
NCOA3	NM_006534.4	c.*1222A>G		3_prime_UTR_variant	23/23		NP_006525.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOA3	ENST00000371998.8	c.*1222A>G		3_prime_UTR_variant	23/23	1	NM_181659.3	ENSP00000361066	P4
NCOA3	ENST00000371997.3	c.*1222A>G		3_prime_UTR_variant	23/23	1		ENSP00000361065	A2
NCOA3	ENST00000372004.7	c.*1222A>G		3_prime_UTR_variant	23/23	1		ENSP00000361073	A2

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

Gnomad4 FIN exome AF: 0.177

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.500

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

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.264

Alfa AF: 0.286 Hom.: 6466

Bravo AF: 0.234

Asia WGS AF: 0.232 AC: 812 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.1
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11699879; hg19: chr20-46283383;