NM_002228.4:c.659delC

Variant names:

• chr1-58782411-CG-C
• NM_002228.4:c.659delC

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP5

The NM_002228.4(JUN):​c.659delC​(p.Pro220ArgfsTer6) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: JUN NM_002228.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.70
• Publications: 1 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-58782411-CG-C is Pathogenic according to our data. Variant chr1-58782411-CG-C is described in ClinVar as Pathogenic. ClinVar VariationId is 1706623.Status of the report is no_assertion_criteria_provided, 0 stars.

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.659delC	p.Pro220ArgfsTer6	frameshift	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.659delC	p.Pro220ArgfsTer6	frameshift	Exon 1 of 1	ENSP00000360266.2	P05412
	JUN	ENST00000710273.1		c.725delC	p.Pro242ArgfsTer6	frameshift	Exon 1 of 1	ENSP00000518166.1	A0AA34QVR9
	JUN	ENST00000678696.1		n.659delC		non_coding_transcript_exon	Exon 1 of 4	ENSP00000503132.1	P05412

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Breast neoplasm (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.7

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

hg19: chr1-59248083; COSMIC: COSV105922685;