rs1537028

Variant names:

• chr20-46062711-T-A
• rs1537028
• NM_020967.3:c.1329A>T

Your query was ambiguous. Multiple possible variants found:

• chr20-46062711-T-A
• chr20-46062711-T-C
• chr20-46062711-T-G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_020967.3(NCOA5):​c.1329A>T​(p.Thr443Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: NCOA5 NM_020967.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.82
• Publications: 29 publications found

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

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP7: Synonymous conserved (PhyloP=-2.82 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOA5	NM_020967.3	c.1329A>T	p.Thr443Thr	synonymous_variant	Exon 8 of 8	ENST00000290231.11	NP_066018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOA5	ENST00000290231.11	c.1329A>T	p.Thr443Thr	synonymous_variant	Exon 8 of 8	1	NM_020967.3	ENSP00000290231.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000116 AC: 17 AN: 1461850 Hom.: 0 Cov.: 61 AF XY: 0.0000179 AC XY: 13 AN XY: 727220

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000719 AC: 8 AN: 1111978

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 11394

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.32
DANN	Benign	0.68
PhyloP100		-2.8

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: rs1537028; hg19: chr20-44691350;