Variant 10-46010581-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001145263.2(NCOA4):c.1340A>G(p.Lys447Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00461 in 1,614,224 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.0035 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0047 ( 27 hom. )

Consequence

NCOA4
NM_001145263.2 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 1.40

Variant links:

Genes affected

NCOA4 (HGNC:7671): (nuclear receptor coactivator 4) This gene encodes an androgen receptor coactivator. The encoded protein interacts with the androgen receptor in a ligand-dependent manner to enhance its transcriptional activity. Chromosomal translocations between this gene and the ret tyrosine kinase gene, also located on chromosome 10, have been associated with papillary thyroid carcinoma. Alternatively spliced transcript variants have been described. Pseudogenes are present on chromosomes 4, 5, 10, and 14. [provided by RefSeq, Feb 2009]

NCOA4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011272341).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOA4	NM_001145263.2 linkuse as main transcript	c.1340A>G	p.Lys447Arg	missense_variant	8/10	ENST00000581486.6	NP_001138735.1	Q13772-1A0A024QZI5B2R5V0Q96E88

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOA4	ENST00000581486.6 linkuse as main transcript	c.1340A>G	p.Lys447Arg	missense_variant	8/10	1	NM_001145263.2	ENSP00000462943.1		Q13772-1

Frequencies

GnomAD3 genomes

AF:

0.00354

AC:

539

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00451

Gnomad ASJ

AF:

0.0181

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00500

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00368

AC:

925

AN:

251236

Hom.:

AF XY:

0.00375

AC XY:

509

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.000743

Gnomad AMR exome

AF:

0.00199

Gnomad ASJ exome

AF:

0.0198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000915

Gnomad FIN exome

AF:

0.000416

Gnomad NFE exome

AF:

0.00516

Gnomad OTH exome

AF:

0.00327

GnomAD4 exome

AF:

0.00473

AC:

6909

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00465

AC XY:

3383

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.00195

Gnomad4 ASJ exome

AF:

0.0179

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000823

Gnomad4 FIN exome

AF:

0.00101

Gnomad4 NFE exome

AF:

0.00535

Gnomad4 OTH exome

AF:

0.00435

GnomAD4 genome

AF:

0.00354

AC:

539

AN:

152338

Hom.:

Cov.:

AF XY:

0.00346

AC XY:

258

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00115

Gnomad4 AMR

AF:

0.00451

Gnomad4 ASJ

AF:

0.0181

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.00500

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00502

Hom.:

Bravo

AF:

0.00365

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not provided

Other:1

not provided, no classification provided

phenotyping only

GenomeConnect, ClinGen

Variant interpretted as Uncertain significance and reported on 10/30/2014 by GTR ID 320384. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.16

T;T;T;T;.;.;.

LIST_S2

Benign

0.66

.;T;T;.;T;T;T

MetaRNN

Benign

0.011

T;T;T;T;T;T;T

Sift4G

Benign

0.12

T;T;T;T;T;T;T

Vest4

0.080

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.10

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over