20-46062711-T-G

Position:

• chr20-46062711-T-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_020967.3(NCOA5):​c.1329A>C​(p.Thr443Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 1,613,796 control chromosomes in the GnomAD database, including 96,895 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 0.32 (8358 hom., cov: 32)
  • Exomes 𝑓: 0.34 (88537 hom.)
• Consequence: NCOA5 NM_020967.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.82

Genes affected

NCOA5 (HGNC:15909): (nuclear receptor coactivator 5) This gene encodes a coregulator for the alpha and beta estrogen receptors and the orphan nuclear receptor NR1D2. The protein localizes to the nucleus, and is thought to have both coactivator and corepressor functions. Its interaction with nuclear receptors is independent of the AF2 domain on the receptors, which is known to regulate interaction with other coreceptors. Several alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2017]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP7: Synonymous conserved (PhyloP=-2.82 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOA5	NM_020967.3	c.1329A>C	p.Thr443Thr	synonymous_variant	8/8	ENST00000290231.11	NP_066018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOA5	ENST00000290231.11	c.1329A>C	p.Thr443Thr	synonymous_variant	8/8	1	NM_020967.3	ENSP00000290231.6

Frequencies

GnomAD3 genomes AF: 0.323 AC: 49095 AN: 151856 Hom.: 8349 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.355

GnomAD3 exomes AF: 0.375 AC: 94263 AN: 251378 Hom.: 19085 AF XY: 0.370 AC XY: 50282 AN XY: 135858

Gnomad AFR exome AF: 0.260

Gnomad AMR exome AF: 0.529

Gnomad ASJ exome AF: 0.334

Gnomad EAS exome AF: 0.576

Gnomad SAS exome AF: 0.374

Gnomad FIN exome AF: 0.274

Gnomad NFE exome AF: 0.336

Gnomad OTH exome AF: 0.367

GnomAD4 exome AF: 0.342 AC: 499902 AN: 1461822 Hom.: 88537 Cov.: 61 AF XY: 0.343 AC XY: 249172 AN XY: 727202

Gnomad4 AFR exome AF: 0.255

Gnomad4 AMR exome AF: 0.514

Gnomad4 ASJ exome AF: 0.331

Gnomad4 EAS exome AF: 0.593

Gnomad4 SAS exome AF: 0.377

Gnomad4 FIN exome AF: 0.281

Gnomad4 NFE exome AF: 0.329

Gnomad4 OTH exome AF: 0.341

GnomAD4 genome AF: 0.323 AC: 49118 AN: 151974 Hom.: 8358 Cov.: 32 AF XY: 0.323 AC XY: 24028 AN XY: 74302

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.569

Gnomad4 SAS AF: 0.375

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.358

Alfa AF: 0.325 Hom.: 8623

Bravo AF: 0.338

Asia WGS AF: 0.492 AC: 1712 AN: 3478

EpiCase AF: 0.335

EpiControl AF: 0.341

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.34
DANN	Benign	0.61

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: rs1537028; hg19: chr20-44691350; COSMIC: COSV51642907; COSMIC: COSV51642907;