10-46010661-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001145263.2(NCOA4):c.1260G>A(p.Glu420=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00414 in 1,614,168 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0032 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0042 (25 hom.)
• Consequence: NCOA4 NM_001145263.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.312

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 10-46010661-C-T is Benign according to our data. Variant chr10-46010661-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2640465.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.312 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCOA4	NM_001145263.2	c.1260G>A	p.Glu420=	synonymous_variant	8/10	ENST00000581486.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCOA4	ENST00000581486.6	c.1260G>A	p.Glu420=	synonymous_variant	8/10	1	NM_001145263.2	P2

Frequencies

GnomAD3 genomes AF: 0.00315 AC: 480 AN: 152172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000869

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00518

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00531

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00270 AC: 679 AN: 251384 Hom.: 2 AF XY: 0.00296 AC XY: 402 AN XY: 135858

Gnomad AFR exome AF: 0.000615

Gnomad AMR exome AF: 0.00121

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00405

Gnomad FIN exome AF: 0.000323

Gnomad NFE exome AF: 0.00422

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00424 AC: 6199 AN: 1461878 Hom.: 25 Cov.: 32 AF XY: 0.00435 AC XY: 3162 AN XY: 727238

Gnomad4 AFR exome AF: 0.000508

Gnomad4 AMR exome AF: 0.00116

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00467

Gnomad4 FIN exome AF: 0.000468

Gnomad4 NFE exome AF: 0.00494

Gnomad4 OTH exome AF: 0.00339

GnomAD4 genome AF: 0.00315 AC: 480 AN: 152290 Hom.: 0 Cov.: 32 AF XY: 0.00326 AC XY: 243 AN XY: 74454

Gnomad4 AFR AF: 0.000866

Gnomad4 AMR AF: 0.00314

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00518

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00531

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00384 Hom.: 1

Bravo AF: 0.00268

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

NCOA4: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	4.8
Dann	Benign	0.68

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: rs112613721; hg19: chr10-51585161;