NM_181659.3:c.1205G>A

Variant names:

• chr20-47635414-G-A
• rs375357603
• NM_181659.3:c.1205G>A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BS2_Supporting

The NM_181659.3(NCOA3):​c.1205G>A​(p.Ser402Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: NCOA3 NM_181659.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.223

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 Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.026164979).
• BS2: High AC in GnomAdExome4 at 6 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOA3	NM_181659.3	c.1205G>A	p.Ser402Asn	missense_variant	Exon 11 of 23	ENST00000371998.8	NP_858045.1
NCOA3	NM_001174087.2	c.1205G>A	p.Ser402Asn	missense_variant	Exon 11 of 23		NP_001167558.1
NCOA3	NM_006534.4	c.1205G>A	p.Ser402Asn	missense_variant	Exon 11 of 23		NP_006525.2
NCOA3	NM_001174088.2	c.1235G>A	p.Ser412Asn	missense_variant	Exon 11 of 23		NP_001167559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOA3	ENST00000371998.8	c.1205G>A	p.Ser402Asn	missense_variant	Exon 11 of 23	1	NM_181659.3	ENSP00000361066.3
NCOA3	ENST00000372004.7	c.1205G>A	p.Ser402Asn	missense_variant	Exon 11 of 23	1		ENSP00000361073.1
NCOA3	ENST00000371997.3	c.1235G>A	p.Ser412Asn	missense_variant	Exon 11 of 23	1		ENSP00000361065.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251318 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135824

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.020
DANN	Benign	0.61
DEOGEN2	Benign	0.035	.;T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.66	T;T;T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.026	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.60	N;N;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.52	N;N;N
REVEL	Benign	0.044
Sift	Benign	0.38	T;T;T
Sift4G	Benign	0.74	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.027
MVP		0.13
MPC		0.10
ClinPred		0.051	T
GERP RS		-3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.025
gMVP		0.17

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: rs375357603; hg19: chr20-46264158;