rs1827361012

Variant names:

• chr9-99828487-C-A
• rs1827361012
• NM_006981.4:c.445C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-99828487-C-A
• chr9-99828487-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006981.4(NR4A3):​c.445C>A​(p.Pro149Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 152,056 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P149S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NR4A3 NM_006981.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.89
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23335391).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR4A3	NM_006981.4	c.445C>A	p.Pro149Thr	missense_variant	Exon 3 of 8	ENST00000395097.7	NP_008912.2
NR4A3	NM_173200.3	c.478C>A	p.Pro160Thr	missense_variant	Exon 4 of 9		NP_775292.1
NR4A3	NM_173199.4	c.445C>A	p.Pro149Thr	missense_variant	Exon 3 of 5		NP_775291.1
NR4A3	XM_017015162.2	c.445C>A	p.Pro149Thr	missense_variant	Exon 4 of 9		XP_016870651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR4A3	ENST00000395097.7	c.445C>A	p.Pro149Thr	missense_variant	Exon 3 of 8	1	NM_006981.4	ENSP00000378531.2

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151942 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1427184 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 707050

African (AFR) AF: 0.00 AC: 0 AN: 32412

American (AMR) AF: 0.00 AC: 0 AN: 39564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23578

East Asian (EAS) AF: 0.00 AC: 0 AN: 39420

South Asian (SAS) AF: 0.00 AC: 0 AN: 80494

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50702

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5584

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1096616

Other (OTH) AF: 0.00 AC: 0 AN: 58814

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152056 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74346

African (AFR) AF: 0.00 AC: 0 AN: 41536

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5140

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67872

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Asia WGS AF: 0.000289 AC: 1 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	.;T;.;.
Eigen	Benign	-0.027
Eigen_PC	Benign	0.094
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.61	T;T;T;.
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.23	T;T;T;T
MetaSVM	Uncertain	-0.041	T
MutationAssessor	Benign	1.1	L;L;.;.
PhyloP100		3.9
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.7	D;D;.;D
REVEL	Uncertain	0.57
Sift	Benign	0.11	T;T;.;T
Sift4G	Benign	0.22	T;T;T;T
Polyphen		0.28	B;B;B;B
Vest4		0.50
MutPred		0.31		Gain of phosphorylation at P149 (P = 0.014);Gain of phosphorylation at P149 (P = 0.014);.;.;
MVP		0.85
ClinPred		0.81	D
GERP RS		4.3
Varity_R		0.30
gMVP		0.25
Mutation Taster		=56/44	polymorphism

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: rs1827361012; hg19: chr9-102590769;