9-99865020-A-G

Variant names:

• chr9-99865020-A-G
• rs1131339
• NM_006981.4:c.*1153A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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]

NAMA (HGNC:42408): (non-protein coding RNA, associated with MAP kinase pathway and growth arrest)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006981.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR4A3	NM_006981.4	MANE Select	c.*1153A>G		3_prime_UTR	Exon 8 of 8	NP_008912.2
	NR4A3	NM_173200.3		c.*1153A>G		3_prime_UTR	Exon 9 of 9	NP_775292.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR4A3	ENST00000395097.7	TSL:1 MANE Select	c.*1153A>G		3_prime_UTR	Exon 8 of 8	ENSP00000378531.2
	NR4A3	ENST00000330847.1	TSL:5	c.*1153A>G		3_prime_UTR	Exon 7 of 7	ENSP00000333122.1
	NR4A3	ENST00000618101.4	TSL:5	c.*1153A>G		3_prime_UTR	Exon 9 of 9	ENSP00000482027.1

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

African (AFR) AF: 0.314 AC: 652 AN: 2078

American (AMR) AF: 0.375 AC: 505 AN: 1348

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1625 AN: 3058

East Asian (EAS) AF: 0.377 AC: 3007 AN: 7984

South Asian (SAS) AF: 0.278 AC: 119 AN: 428

European-Finnish (FIN) AF: 0.480 AC: 220 AN: 458

Middle Eastern (MID) AF: 0.534 AC: 156 AN: 292

European-Non Finnish (NFE) AF: 0.557 AC: 16461 AN: 29570

Other (OTH) AF: 0.504 AC: 2048 AN: 4066

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

African (AFR) AF: 0.303 AC: 12575 AN: 41474

American (AMR) AF: 0.425 AC: 6482 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 1868 AN: 3468

East Asian (EAS) AF: 0.361 AC: 1864 AN: 5170

South Asian (SAS) AF: 0.280 AC: 1349 AN: 4820

European-Finnish (FIN) AF: 0.465 AC: 4902 AN: 10532

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.559 AC: 37949 AN: 67932

Other (OTH) AF: 0.485 AC: 1023 AN: 2110

Alfa AF: 0.519 Hom.: 57961

Bravo AF: 0.448

Asia WGS AF: 0.323 AC: 1124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	11
DANN	Benign	0.85
PhyloP100		5.2
Mutation Taster		=100/0	polymorphism (auto)

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