chr10-46009179-C-T

Variant names:

• chr10-46009179-C-T
• rs1183208806
• ENST00000578454.5:c.1921G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001145260.2(NCOA4):​c.1921G>A​(p.Val641Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000179 in 1,398,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 7/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: NCOA4 NM_001145260.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.09
• Publications: 0 publications found

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]

ENSG00000289092 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.080311894).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145260.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOA4	NM_001145263.2	MANE Select	c.1839+232G>A		intron	N/A	NP_001138735.1	Q13772-1
	NCOA4	NM_001145260.2		c.1921G>A	p.Val641Ile	missense	Exon 11 of 12	NP_001138732.1	Q13772-4
	NCOA4	NM_001145261.2		c.1887+232G>A		intron	N/A	NP_001138733.1	Q13772-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOA4	ENST00000578454.5	TSL:1	c.1921G>A	p.Val641Ile	missense	Exon 11 of 12	ENSP00000463027.1	Q13772-4
	NCOA4	ENST00000581486.6	TSL:1 MANE Select	c.1839+232G>A		intron	N/A	ENSP00000462943.1	Q13772-1
	NCOA4	ENST00000585132.5	TSL:1	c.1839+232G>A		intron	N/A	ENSP00000464054.1	Q13772-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000179 AC: 25 AN: 1398832 Hom.: 0 Cov.: 30 AF XY: 0.0000174 AC XY: 12 AN XY: 689956

African (AFR) AF: 0.00 AC: 0 AN: 31592

American (AMR) AF: 0.000112 AC: 4 AN: 35708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25174

East Asian (EAS) AF: 0.000252 AC: 9 AN: 35718

South Asian (SAS) AF: 0.0000252 AC: 2 AN: 79226

European-Finnish (FIN) AF: 0.0000203 AC: 1 AN: 49270

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5662

European-Non Finnish (NFE) AF: 0.00000834 AC: 9 AN: 1078506

Other (OTH) AF: 0.00 AC: 0 AN: 57976

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.77
LIST_S2	Benign	0.39	T
MetaRNN	Benign	0.080	T
PhyloP100		-1.1
Vest4		0.11
gMVP		0.36
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs1183208806; hg19: chr10-51586643;