NM_181659.3:c.328A>G

Variant names:

• chr20-47625452-A-G
• NM_181659.3:c.328A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_181659.3(NCOA3):​c.328A>G​(p.Lys110Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NCOA3 NM_181659.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.49
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38642177).

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.328A>G	p.Lys110Glu	missense	Exon 5 of 23	NP_858045.1	Q9Y6Q9-1
	NCOA3	NM_001174087.2		c.328A>G	p.Lys110Glu	missense	Exon 5 of 23	NP_001167558.1
	NCOA3	NM_006534.4		c.328A>G	p.Lys110Glu	missense	Exon 5 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.328A>G	p.Lys110Glu	missense	Exon 5 of 23	ENSP00000361066.3	Q9Y6Q9-1
	NCOA3	ENST00000372004.7	TSL:1	c.328A>G	p.Lys110Glu	missense	Exon 5 of 23	ENSP00000361073.1	Q9Y6Q9-5
	NCOA3	ENST00000371997.3	TSL:1	c.328A>G	p.Lys110Glu	missense	Exon 5 of 23	ENSP00000361065.3	Q9Y6Q9-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.52	D
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.9	L
PhyloP100		7.5
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.020	D
Polyphen		1.0	D
Vest4		0.48
MutPred		0.40		Loss of ubiquitination at K110 (P = 0.0077)
MVP		0.78
MPC		0.32
ClinPred		0.99	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.78
gMVP		0.53
Mutation Taster		=62/38	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

hg19: chr20-46254196;