chr10-46010397-G-A

Variant names:

• chr10-46010397-G-A
• rs79761167
• NM_001145263.2:c.1524C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001145263.2(NCOA4):​c.1524C>T​(p.Pro508Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P508P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NCOA4 NM_001145263.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.928
• Publications: 5 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]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP7: Synonymous conserved (PhyloP=0.928 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145263.2. 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.1524C>T	p.Pro508Pro	synonymous	Exon 8 of 10	NP_001138735.1	Q13772-1
	NCOA4	NM_001145260.2		c.1572C>T	p.Pro524Pro	synonymous	Exon 9 of 12	NP_001138732.1	Q13772-4
	NCOA4	NM_001145261.2		c.1572C>T	p.Pro524Pro	synonymous	Exon 9 of 11	NP_001138733.1	Q13772-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOA4	ENST00000581486.6	TSL:1 MANE Select	c.1524C>T	p.Pro508Pro	synonymous	Exon 8 of 10	ENSP00000462943.1	Q13772-1
	NCOA4	ENST00000578454.5	TSL:1	c.1572C>T	p.Pro524Pro	synonymous	Exon 9 of 12	ENSP00000463027.1	Q13772-4
	NCOA4	ENST00000585132.5	TSL:1	c.1524C>T	p.Pro508Pro	synonymous	Exon 8 of 10	ENSP00000464054.1	Q13772-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	4.5
DANN	Benign	0.58
PhyloP100		0.93
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs79761167; hg19: chr10-51585425;