9-99823263-T-C

Position:

• chr9-99823263-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.-177+856T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 149,770 control chromosomes in the GnomAD database, including 8,198 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 0.33 (8198 hom., cov: 30)
• Consequence: NR4A3 NM_006981.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR4A3	NM_006981.4	c.-177+856T>C		intron_variant		ENST00000395097.7	NP_008912.2
NR4A3	NM_173200.3	c.-216+856T>C		intron_variant			NP_775292.1
NR4A3	NM_173199.4	c.-177+856T>C		intron_variant			NP_775291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR4A3	ENST00000395097.7	c.-177+856T>C		intron_variant		1	NM_006981.4	ENSP00000378531.2
NR4A3	ENST00000338488.8	c.-177+856T>C		intron_variant		1		ENSP00000340301.4
NR4A3	ENST00000618101.4	c.-216+856T>C		intron_variant		5		ENSP00000482027.1
STX17-DT	ENST00000655615.1	n.268+15723A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49064 AN: 149654 Hom.: 8196 Cov.: 30

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.328 AC: 49080 AN: 149770 Hom.: 8198 Cov.: 30 AF XY: 0.320 AC XY: 23364 AN XY: 73056

Gnomad4 AFR AF: 0.306

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.416

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.369

Gnomad4 OTH AF: 0.347

Alfa AF: 0.354 Hom.: 14001

Bravo AF: 0.323

Asia WGS AF: 0.201 AC: 701 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.9
DANN	Benign	0.49

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: rs1405209; hg19: chr9-102585545;