9-99865020-A-G

Position:

• chr9-99865020-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006981.4(NR4A3):​c.*1153A>G variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.465 in 201,244 control chromosomes in the GnomAD database, including 23,138 homozygotes. 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: 𝑓 0.45 (16696 hom., cov: 31)
  • Exomes 𝑓: 0.50 (6442 hom.)
• Consequence: NR4A3 NM_006981.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.18

Genes affected

NR4A3 (HGNC:7982): (nuclear receptor subfamily 4 group A member 3) This gene encodes a member of the steroid-thyroid hormone-retinoid receptor superfamily. The encoded protein may act as a transcriptional activator. The protein can efficiently bind the NGFI-B Response Element (NBRE). Three different versions of extraskeletal myxoid chondrosarcomas (EMCs) are the result of reciprocal translocations between this gene and other genes. The translocation breakpoints are associated with Nuclear Receptor Subfamily 4, Group A, Member 3 (on chromosome 9) and either Ewing Sarcome Breakpoint Region 1 (on chromosome 22), RNA Polymerase II, TATA Box-Binding Protein-Associated Factor, 68-KD (on chromosome 17), or Transcription factor 12 (on chromosome 15). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]

STX17-DT (HGNC:51174): (STX17 divergent transcript)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR4A3	NM_006981.4	c.*1153A>G		3_prime_UTR_variant	8/8	ENST00000395097.7
NR4A3	NM_173200.3	c.*1153A>G		3_prime_UTR_variant	9/9
NR4A3	XM_017015162.2	c.*1153A>G		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR4A3	ENST00000395097.7	c.*1153A>G		3_prime_UTR_variant	8/8	1	NM_006981.4	P1
STX17-DT	ENST00000655615.1	n.179-25945T>C		intron_variant, non_coding_transcript_variant
NR4A3	ENST00000330847.1	c.*1153A>G		3_prime_UTR_variant	7/7	5
NR4A3	ENST00000618101.4	c.*1153A>G		3_prime_UTR_variant	9/9	5

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68712 AN: 151844 Hom.: 16689 Cov.: 31

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.490

GnomAD4 exome AF: 0.503 AC: 24793 AN: 49282 Hom.: 6442 Cov.: 0 AF XY: 0.507 AC XY: 11573 AN XY: 22804

Gnomad4 AFR exome AF: 0.314

Gnomad4 AMR exome AF: 0.375

Gnomad4 ASJ exome AF: 0.531

Gnomad4 EAS exome AF: 0.377

Gnomad4 SAS exome AF: 0.278

Gnomad4 FIN exome AF: 0.480

Gnomad4 NFE exome AF: 0.557

Gnomad4 OTH exome AF: 0.504

GnomAD4 genome AF: 0.452 AC: 68730 AN: 151962 Hom.: 16696 Cov.: 31 AF XY: 0.443 AC XY: 32884 AN XY: 74242

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.425

Gnomad4 ASJ AF: 0.539

Gnomad4 EAS AF: 0.361

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.559

Gnomad4 OTH AF: 0.485

Alfa AF: 0.539 Hom.: 36941

Bravo AF: 0.448

Asia WGS AF: 0.323 AC: 1124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	11
DANN	Benign	0.85

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: rs1131339; hg19: chr9-102627302; COSMIC: COSV58243713;