9-99851390-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006981.4(NR4A3):c.1633+3775T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0793 in 152,290 control chromosomes in the GnomAD database, including 620 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 0.079 (620 hom., cov: 32)
• Consequence: NR4A3 NM_006981.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.08

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR4A3	NM_006981.4	c.1633+3775T>C		intron_variant		ENST00000395097.7
NR4A3	NM_173200.3	c.1666+3775T>C		intron_variant
NR4A3	XM_017015162.2	c.1633+3775T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR4A3	ENST00000395097.7	c.1633+3775T>C		intron_variant		1	NM_006981.4	P1
STX17-DT	ENST00000655615.1	n.179-12315A>G		intron_variant, non_coding_transcript_variant
NR4A3	ENST00000330847.1	c.1666+3775T>C		intron_variant		5
NR4A3	ENST00000618101.4	c.1666+3775T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0794 AC: 12075 AN: 152172 Hom.: 618 Cov.: 32

Gnomad AFR AF: 0.0206

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0899

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.0565

Gnomad SAS AF: 0.0516

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.0865

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0793 AC: 12084 AN: 152290 Hom.: 620 Cov.: 32 AF XY: 0.0788 AC XY: 5867 AN XY: 74466

Gnomad4 AFR AF: 0.0205

Gnomad4 AMR AF: 0.0902

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.0568

Gnomad4 SAS AF: 0.0518

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.0866

Alfa AF: 0.0853 Hom.: 356

Bravo AF: 0.0757

Asia WGS AF: 0.0550 AC: 189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	11
Dann	Benign	0.78

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: rs2416879; hg19: chr9-102613672;