chr9-128694007-G-GA

Position:

• chr9-128694007-G-GA

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_Moderate PM2

The NM_003011.4(SET):​c.777dup​(p.Asp260ArgfsTer2) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as other (no stars).

• Frequency: Genomes: not found (cov: 29)
• Consequence: SET NM_003011.4 frameshift
• Clinical Significance: other no assertion criteria provided O:1
• Conservation: PhyloP100: 6.38

Genes affected

SET (HGNC:10760): (SET nuclear proto-oncogene) The protein encoded by this gene inhibits acetylation of nucleosomes, especially histone H4, by histone acetylases (HAT). This inhibition is most likely accomplished by masking histone lysines from being acetylated, and the consequence is to silence HAT-dependent transcription. The encoded protein is part of a complex localized to the endoplasmic reticulum but is found in the nucleus and inhibits apoptosis following attack by cytotoxic T lymphocytes. This protein can also enhance DNA replication of the adenovirus genome. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0707 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SET	NM_003011.4	c.777dup	p.Asp260ArgfsTer2	frameshift_variant	7/8	ENST00000322030.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SET	ENST00000322030.13	c.777dup	p.Asp260ArgfsTer2	frameshift_variant	7/8	1	NM_003011.4	P1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 29

ClinVar

Significance: other

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Dysgerminoma Other:1

other, no assertion criteria provided

clinical testing

Donald Williams Parsons Laboratory, Baylor College of Medicine

May 01, 2016

- 3: Mutations in other consensus cancer genes, not currently considered targetable

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.37		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.37		Position offset: -6

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

Publications

LitVar

Other links and lift over

dbSNP: rs1554777032; hg19: chr9-131456286;