chr9-99828486-C-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_006981.4(NR4A3):c.444C>A(p.Phe148Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000253 in 1,577,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

NR4A3
NM_006981.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.35

Publications

1 publications found

Variant links:

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]

NR4A3 links:

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

NAMA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07321808).

BS2

High AC in GnomAd4 at 5 AD gene.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NR4A3	NM_006981.4	MANE Select	c.444C>A	p.Phe148Leu	missense	Exon 3 of 8	NP_008912.2
NR4A3	NM_173200.3		c.477C>A	p.Phe159Leu	missense	Exon 4 of 9	NP_775292.1	Q92570-3
NR4A3	NM_173199.4		c.444C>A	p.Phe148Leu	missense	Exon 3 of 5	NP_775291.1	Q92570-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NR4A3	ENST00000395097.7	TSL:1 MANE Select	c.444C>A	p.Phe148Leu	missense	Exon 3 of 8	ENSP00000378531.2	Q92570-1
NR4A3	ENST00000338488.8	TSL:1	c.444C>A	p.Phe148Leu	missense	Exon 3 of 5	ENSP00000340301.4	Q92570-2
NR4A3	ENST00000330847.1	TSL:5	c.477C>A	p.Phe159Leu	missense	Exon 2 of 7	ENSP00000333122.1	Q92570-3

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

151868

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000972

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

GnomAD2 exomes

AF:

0.0000630

AC:

AN:

206388

AF XY:

0.0000533

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000722

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000245

AC:

AN:

1426106

Hom.:

Cov.:

AF XY:

0.0000198

AC XY:

AN XY:

706392

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32414

American (AMR)

AF:

0.00

AC:

AN:

39476

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23502

East Asian (EAS)

AF:

0.000432

AC:

AN:

39390

South Asian (SAS)

AF:

0.00

AC:

AN:

80292

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5584

European-Non Finnish (NFE)

AF:

9.12e-7

AC:

AN:

1096102

Other (OTH)

AF:

0.000289

AC:

AN:

58766

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000329

AC:

AN:

151868

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74204

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41404

American (AMR)

AF:

0.00

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.000972

AC:

AN:

5142

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67856

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.0000586

AC:

Asia WGS

AF:

0.000867

AC:

AN:

3476

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.11

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.62

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.72

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.073

MetaSVM

Benign

-0.46

MutationAssessor

Benign

1.3

PhyloP100

1.4

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-2.9

REVEL

Uncertain

0.38

Sift

Benign

0.055

Sift4G

Benign

0.13

Polyphen

0.055

Vest4

0.24

MutPred

0.28

Gain of glycosylation at P149 (P = 0.1628)

MVP

0.82

ClinPred

0.19

GERP RS

2.8

Varity_R

0.27

gMVP

0.21

Mutation Taster

=84/16

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over