chr7-100200852-C-CCT

Variant names:

• chr7-100200852-C-CCT
• rs869320765
• NM_001282717.2:c.1947_1948dupCT

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001282717.2(STAG3):​c.1947_1948dupCT​(p.Tyr650SerfsTer22) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: STAG3 NM_001282717.2 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 1.45
• Publications: 5 publications found

Genes affected

STAG3 (HGNC:11356): (STAG3 cohesin complex component) The protein encoded by this gene is expressed in the nucleus and is a subunit of the cohesin complex which regulates the cohesion of sister chromatids during cell division. A mutation in this gene is associated with premature ovarian failure. Alternate splicing results in multiple transcript variants encoding distinct isoforms. This gene has multiple pseudogenes. [provided by RefSeq, Apr 2014]

CASTOR3P (HGNC:):

CASTOR3P (HGNC:29954): (CASTOR family member 3, pseudogene) Predicted to be involved in cellular response to L-arginine and negative regulation of TORC1 signaling. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Pathogenic. The variant received 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 7-100200852-C-CCT is Pathogenic according to our data. Variant chr7-100200852-C-CCT is described in ClinVar as Pathogenic. ClinVar VariationId is 224903.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282717.2. 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
	STAG3	NM_001282717.2	MANE Select	c.1947_1948dupCT	p.Tyr650SerfsTer22	frameshift	Exon 19 of 34	NP_001269646.1	D6W5U7
	STAG3	NM_001375438.1		c.1947_1948dupCT	p.Tyr650SerfsTer22	frameshift	Exon 19 of 34	NP_001362367.1	D6W5U7
	STAG3	NM_001282716.1		c.1947_1948dupCT	p.Tyr650SerfsTer22	frameshift	Exon 19 of 34	NP_001269645.1	Q9UJ98-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAG3	ENST00000615138.5	TSL:1 MANE Select	c.1947_1948dupCT	p.Tyr650SerfsTer22	frameshift	Exon 19 of 34	ENSP00000477973.1	D6W5U7
	STAG3	ENST00000317296.9	TSL:1	c.1947_1948dupCT	p.Tyr650SerfsTer22	frameshift	Exon 19 of 34	ENSP00000319318.5	Q9UJ98-1
	STAG3	ENST00000426455.5	TSL:1	c.1947_1948dupCT	p.Tyr650SerfsTer22	frameshift	Exon 19 of 34	ENSP00000400359.1	Q9UJ98-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Premature ovarian failure 8 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5
Mutation Taster		=1/199	disease causing (ClinVar)

Splicing

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

Other links and lift over

dbSNP: rs869320765; hg19: chr7-99798475;