NM_181659.3:c.836A>C

Variant names:

• chr20-47633508-A-C
• NM_181659.3:c.836A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_181659.3(NCOA3):​c.836A>C​(p.Asn279Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NCOA3 NM_181659.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.23

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16082668).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOA3	NM_181659.3	c.836A>C	p.Asn279Thr	missense_variant	Exon 9 of 23	ENST00000371998.8	NP_858045.1
NCOA3	NM_001174087.2	c.836A>C	p.Asn279Thr	missense_variant	Exon 9 of 23		NP_001167558.1
NCOA3	NM_006534.4	c.836A>C	p.Asn279Thr	missense_variant	Exon 9 of 23		NP_006525.2
NCOA3	NM_001174088.2	c.836A>C	p.Asn279Thr	missense_variant	Exon 9 of 23		NP_001167559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOA3	ENST00000371998.8	c.836A>C	p.Asn279Thr	missense_variant	Exon 9 of 23	1	NM_181659.3	ENSP00000361066.3
NCOA3	ENST00000372004.7	c.836A>C	p.Asn279Thr	missense_variant	Exon 9 of 23	1		ENSP00000361073.1
NCOA3	ENST00000371997.3	c.836A>C	p.Asn279Thr	missense_variant	Exon 9 of 23	1		ENSP00000361065.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.068	.;T;.
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.39
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.58	T;T;T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;L;L
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.037
Sift	Benign	0.032	D;D;D
Sift4G	Benign	0.13	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.28
MutPred		0.51		Gain of ubiquitination at K276 (P = 0.0566);Gain of ubiquitination at K276 (P = 0.0566);Gain of ubiquitination at K276 (P = 0.0566);
MVP		0.31
MPC		0.11
ClinPred		0.15	T
GERP RS		1.5
Varity_R		0.067
gMVP		0.42

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-46262252;