rs1553722294

Positions:

• chr3-136443368-A-ATAAAC

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_005862.3(STAG1):​c.1464_1465insGTTTA​(p.Trp489ValfsTer10) 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 Likely pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: STAG1 NM_005862.3 frameshift
• Clinical Significance: Pathogenic/Likely pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: 1.44

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 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 3-136443368-A-ATAAAC is Pathogenic according to our data. Variant chr3-136443368-A-ATAAAC is described in ClinVar as [Likely_pathogenic]. Clinvar id is 437900.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAG1	NM_005862.3	c.1464_1465insGTTTA	p.Trp489ValfsTer10	frameshift_variant	15/34	ENST00000383202.7	NP_005853.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAG1	ENST00000383202.7	c.1464_1465insGTTTA	p.Trp489ValfsTer10	frameshift_variant	15/34	1	NM_005862.3	ENSP00000372689	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

Submissions by phenotype

Intellectual disability, autosomal dominant 47 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 25, 2022

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1553722294; hg19: chr3-136162210;