rs193920792

Variant names:

• chr13-43355976-GCGGGGAT-G
• rs193920792
• NM_001347969.2:c.759_765delATCCCCG

Variant summary

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

The NM_001347969.2(ENOX1):​c.759_765delATCCCCG​(p.Ser254LeufsTer3) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ENOX1 NM_001347969.2 frameshift
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 9.59
• Publications: 0 publications found

Genes affected

ENOX1 (HGNC:25474): (ecto-NOX disulfide-thiol exchanger 1) The protein encoded by this gene is involved in plasma membrane electron transport pathways. The encoded protein has both a hydroquinone (NADH) oxidase activity and a protein disulfide-thiol interchange activity. The two activities cycle with a periodicity of 24 minutes, with one activity being at its peak when the other is at its lowest. [provided by RefSeq, Dec 2016]

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_001347969.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENOX1	NM_001347969.2	MANE Select	c.759_765delATCCCCG	p.Ser254LeufsTer3	frameshift	Exon 8 of 17	NP_001334898.1
	ENOX1	NM_001347963.2		c.864_870delATCCCCG	p.Ser289LeufsTer3	frameshift	Exon 7 of 16	NP_001334892.1
	ENOX1	NM_001127615.3		c.759_765delATCCCCG	p.Ser254LeufsTer3	frameshift	Exon 8 of 17	NP_001121087.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENOX1	ENST00000690772.1	MANE Select	c.759_765delATCCCCG	p.Ser254LeufsTer3	frameshift	Exon 8 of 17	ENSP00000509229.1
	ENOX1	ENST00000261488.10	TSL:1	c.759_765delATCCCCG	p.Ser254LeufsTer3	frameshift	Exon 8 of 17	ENSP00000261488.6

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs193920792; hg19: chr13-43930112; COSMIC: COSV54910764; COSMIC: COSV54910764;