rs764932304

Variant names:

• chr9-99828621-C-A
• rs764932304
• NM_006981.4:c.579C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-99828621-C-A
• chr9-99828621-C-G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_006981.4(NR4A3):​c.579C>A​(p.Phe193Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000402 in 1,491,406 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: NR4A3 NM_006981.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.01
• 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.29305327).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR4A3	NM_006981.4	c.579C>A	p.Phe193Leu	missense_variant	Exon 3 of 8	ENST00000395097.7	NP_008912.2
NR4A3	NM_173200.3	c.612C>A	p.Phe204Leu	missense_variant	Exon 4 of 9		NP_775292.1
NR4A3	NM_173199.4	c.579C>A	p.Phe193Leu	missense_variant	Exon 3 of 5		NP_775291.1
NR4A3	XM_017015162.2	c.579C>A	p.Phe193Leu	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.579C>A	p.Phe193Leu	missense_variant	Exon 3 of 8	1	NM_006981.4	ENSP00000378531.2

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151788 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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: 0.0000114 AC: 1 AN: 87616 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000622

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000299 AC: 4 AN: 1339510 Hom.: 0 Cov.: 31 AF XY: 0.00000302 AC XY: 2 AN XY: 661510

African (AFR) AF: 0.0000371 AC: 1 AN: 26968

American (AMR) AF: 0.0000717 AC: 2 AN: 27900

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23112

East Asian (EAS) AF: 0.00 AC: 0 AN: 29814

South Asian (SAS) AF: 0.00 AC: 0 AN: 74240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34060

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4670

European-Non Finnish (NFE) AF: 9.41e-7 AC: 1 AN: 1063136

Other (OTH) AF: 0.00 AC: 0 AN: 55610

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151896 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74250

African (AFR) AF: 0.0000482 AC: 2 AN: 41514

American (AMR) AF: 0.00 AC: 0 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10514

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67860

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000121 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Uncertain	0.084	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.52	.;D;.;.
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.075
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.91	D;D;D;.
M_CAP	Pathogenic	0.87	D
MetaRNN	Benign	0.29	T;T;T;T
MetaSVM	Benign	-0.34	T
MutationAssessor	Benign	0.81	L;L;.;.
PhyloP100		3.0
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-2.1	N;N;.;N
REVEL	Uncertain	0.41
Sift	Benign	0.092	T;T;.;T
Sift4G	Benign	0.14	T;T;T;T
Polyphen		0.33	B;B;B;B
Vest4		0.36
MutPred		0.20		Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);.;.;
MVP		0.91
ClinPred		0.13	T
GERP RS		2.9
Varity_R		0.16
gMVP		0.52
Mutation Taster		=82/18	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: rs764932304; hg19: chr9-102590903;