rs1553718528

chr3-136422958-C-CA

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_005862.3(STAG1):c.1736_1737insT(p.Ser580ValfsTer21) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. L579L) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: STAG1 NM_005862.3 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter P:2 U:1
• Conservation: PhyloP100: 6.97

Genes affected

STAG1 (HGNC:11354): (STAG1 cohesin complex component) This gene is a member of the SCC3 family and is expressed in the nucleus. It encodes a component of cohesin, a multisubunit protein complex that provides sister chromatid cohesion along the length of a chromosome from DNA replication through prophase and prometaphase, after which it is dissociated in preparation for segregation during anaphase. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Pathogenic. Variant got 10 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAG1	NM_005862.3	c.1736_1737insT	p.Ser580ValfsTer21	frameshift_variant	17/34	ENST00000383202.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAG1	ENST00000383202.7	c.1736_1737insT	p.Ser580ValfsTer21	frameshift_variant	17/34	1	NM_005862.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:2 Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual disability, autosomal dominant 47 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 31, 2017

- -

STAG1-related disorder Pathogenic:1

Likely pathogenic, no assertion criteria provided

clinical testing

Equipe Genetique des Anomalies du Developpement, Université de Bourgogne

Dec 20, 2016

- -

Intellectual disability Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Diagnostic Laboratory, Strasbourg University Hospital

Sep 10, 2020

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs1553718528; hg19: chr3-136141800;