chr20-47627680-C-T

Position:

• chr20-47627680-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181659.3(NCOA3):​c.652C>T​(p.Arg218Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0449 in 1,613,884 control chromosomes in the GnomAD database, including 1,914 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.051 (234 hom., cov: 32)
  • Exomes 𝑓: 0.044 (1680 hom.)
• Consequence: NCOA3 NM_181659.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.41

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]

NCOA3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0030201674).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOA3	NM_181659.3	c.652C>T	p.Arg218Cys	missense_variant	7/23	ENST00000371998.8	NP_858045.1
NCOA3	NM_001174087.2	c.652C>T	p.Arg218Cys	missense_variant	7/23		NP_001167558.1
NCOA3	NM_006534.4	c.652C>T	p.Arg218Cys	missense_variant	7/23		NP_006525.2
NCOA3	NM_001174088.2	c.652C>T	p.Arg218Cys	missense_variant	7/23		NP_001167559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOA3	ENST00000371998.8	c.652C>T	p.Arg218Cys	missense_variant	7/23	1	NM_181659.3	ENSP00000361066.3
NCOA3	ENST00000372004.7	c.652C>T	p.Arg218Cys	missense_variant	7/23	1		ENSP00000361073.1
NCOA3	ENST00000371997.3	c.652C>T	p.Arg218Cys	missense_variant	7/23	1		ENSP00000361065.3
NCOA3	ENST00000497292.1	n.295C>T		non_coding_transcript_exon_variant	2/4	5

Frequencies

GnomAD3 genomes AF: 0.0514 AC: 7815 AN: 152118 Hom.: 234 Cov.: 32

Gnomad AFR AF: 0.0696

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.0488

Gnomad ASJ AF: 0.0297

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0495

Gnomad FIN AF: 0.0351

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0477

Gnomad OTH AF: 0.0564

GnomAD3 exomes AF: 0.0410 AC: 10311 AN: 251198 Hom.: 247 AF XY: 0.0430 AC XY: 5832 AN XY: 135746

Gnomad AFR exome AF: 0.0681

Gnomad AMR exome AF: 0.0297

Gnomad ASJ exome AF: 0.0287

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0513

Gnomad FIN exome AF: 0.0341

Gnomad NFE exome AF: 0.0464

Gnomad OTH exome AF: 0.0503

GnomAD4 exome AF: 0.0442 AC: 64585 AN: 1461650 Hom.: 1680 Cov.: 32 AF XY: 0.0452 AC XY: 32885 AN XY: 727134

Gnomad4 AFR exome AF: 0.0656

Gnomad4 AMR exome AF: 0.0304

Gnomad4 ASJ exome AF: 0.0268

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0531

Gnomad4 FIN exome AF: 0.0341

Gnomad4 NFE exome AF: 0.0455

Gnomad4 OTH exome AF: 0.0457

GnomAD4 genome AF: 0.0513 AC: 7815 AN: 152234 Hom.: 234 Cov.: 32 AF XY: 0.0503 AC XY: 3745 AN XY: 74442

Gnomad4 AFR AF: 0.0694

Gnomad4 AMR AF: 0.0487

Gnomad4 ASJ AF: 0.0297

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0504

Gnomad4 FIN AF: 0.0351

Gnomad4 NFE AF: 0.0476

Gnomad4 OTH AF: 0.0558

Alfa AF: 0.0488 Hom.: 456

Bravo AF: 0.0529

TwinsUK AF: 0.0458 AC: 170

ALSPAC AF: 0.0446 AC: 172

ESP6500AA AF: 0.0658 AC: 290

ESP6500EA AF: 0.0472 AC: 406

ExAC AF: 0.0423 AC: 5142

Asia WGS AF: 0.0230 AC: 80 AN: 3478

EpiCase AF: 0.0530

EpiControl AF: 0.0525

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.44	.;T;.
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.42	T;T;T
MetaRNN	Benign	0.0030	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M;M;M
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.4	D;D;D
REVEL	Benign	0.20
Sift	Benign	0.18	T;T;T
Sift4G	Uncertain	0.057	T;T;T
Polyphen		0.56	P;B;D
Vest4		0.57
MPC		0.50
ClinPred		0.045	T
GERP RS		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.36
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs6094752; hg19: chr20-46256424; COSMIC: COSV59066261; COSMIC: COSV59066261;