1-58782790-G-A

Variant names:

• chr1-58782790-G-A
• rs2100739777
• NM_002228.4:c.281C>T

Variant summary

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

The NM_002228.4(JUN):​c.281C>T​(p.Pro94Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. P94R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: JUN NM_002228.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.74
• Publications: 0 publications found

Genes affected

JUN (HGNC:6204): (Jun proto-oncogene, AP-1 transcription factor subunit) This gene is the putative transforming gene of avian sarcoma virus 17. It encodes a protein which is highly similar to the viral protein, and which interacts directly with specific target DNA sequences to regulate gene expression. This gene is intronless and is mapped to 1p32-p31, a chromosomal region involved in both translocations and deletions in human malignancies. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002228.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JUN	NM_002228.4	MANE Select	c.281C>T	p.Pro94Leu	missense	Exon 1 of 1	NP_002219.1	P05412

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JUN	ENST00000371222.4	TSL:6 MANE Select	c.281C>T	p.Pro94Leu	missense	Exon 1 of 1	ENSP00000360266.2	P05412
	JUN	ENST00000710273.1		c.347C>T	p.Pro116Leu	missense	Exon 1 of 1	ENSP00000518166.1	A0AA34QVR9
	JUN	ENST00000678696.1		n.281C>T		non_coding_transcript_exon	Exon 1 of 4	ENSP00000503132.1	P05412

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Benign	0.68	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.66	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		7.7
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-5.7	D
REVEL	Uncertain	0.29
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.86	P
Vest4		0.54
MutPred		0.64		Loss of glycosylation at P94 (P = 0.0191)
MVP		0.80
MPC		2.0
ClinPred		1.0	D
GERP RS		2.2
Varity_R		0.47
gMVP		0.85
Mutation Taster		=46/54	disease causing

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: rs2100739777; hg19: chr1-59248462;