20-47579861-G-T

Variant names:

• chr20-47579861-G-T
• rs6125048
• NM_181659.3:c.-98-3322G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181659.3(NCOA3):​c.-98-3322G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0525 in 152,240 control chromosomes in the GnomAD database, including 952 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 0.053 (952 hom., cov: 32)
• Consequence: NCOA3 NM_181659.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• Publications: 12 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOA3	NM_181659.3	c.-98-3322G>T		intron_variant	Intron 1 of 22	ENST00000371998.8	NP_858045.1
NCOA3	NM_001174087.2	c.-98-3322G>T		intron_variant	Intron 1 of 22		NP_001167558.1
NCOA3	NM_006534.4	c.-98-3322G>T		intron_variant	Intron 1 of 22		NP_006525.2
NCOA3	NM_001174088.2	c.-98-3322G>T		intron_variant	Intron 1 of 22		NP_001167559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOA3	ENST00000371998.8	c.-98-3322G>T		intron_variant	Intron 1 of 22	1	NM_181659.3	ENSP00000361066.3
NCOA3	ENST00000372004.7	c.-98-3322G>T		intron_variant	Intron 1 of 22	1		ENSP00000361073.1
NCOA3	ENST00000371997.3	c.-98-3322G>T		intron_variant	Intron 1 of 22	1		ENSP00000361065.3

Frequencies

GnomAD3 genomes AF: 0.0526 AC: 7995 AN: 152122 Hom.: 951 Cov.: 32

Gnomad AFR AF: 0.0255

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0546

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00516

Gnomad OTH AF: 0.0550

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0525 AC: 7996 AN: 152240 Hom.: 952 Cov.: 32 AF XY: 0.0601 AC XY: 4474 AN XY: 74438

African (AFR) AF: 0.0254 AC: 1056 AN: 41562

American (AMR) AF: 0.211 AC: 3232 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00893 AC: 31 AN: 3472

East Asian (EAS) AF: 0.399 AC: 2059 AN: 5156

South Asian (SAS) AF: 0.117 AC: 565 AN: 4826

European-Finnish (FIN) AF: 0.0546 AC: 579 AN: 10608

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.00516 AC: 351 AN: 68012

Other (OTH) AF: 0.0530 AC: 112 AN: 2112

Alfa AF: 0.0307 Hom.: 1679

Bravo AF: 0.0678

Asia WGS AF: 0.232 AC: 805 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.52
DANN	Benign	0.21
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6125048; hg19: chr20-46208605;