rs371093379

Variant names:

• chr3-136338435-G-A
• NM_005862.3:c.3688C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-136338435-G-A
• chr3-136338435-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP2 BP4

The NM_005862.3(STAG1):​c.3688C>T​(p.Arg1230Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: STAG1 NM_005862.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.61

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the STAG1 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 15 curated pathogenic missense variants (we use a threshold of 10). The gene has 24 curated benign missense variants. Gene score misZ: 4.4429 (above the threshold of 3.09). Trascript score misZ: 4.1606 (above the threshold of 3.09). GenCC associations: The gene is linked to complex neurodevelopmental disorder, intellectual disability, autosomal dominant 47.
• BP4: Computational evidence support a benign effect (MetaRNN=0.32566828).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAG1	NM_005862.3	c.3688C>T	p.Arg1230Trp	missense_variant	Exon 33 of 34	ENST00000383202.7	NP_005853.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAG1	ENST00000383202.7	c.3688C>T	p.Arg1230Trp	missense_variant	Exon 33 of 34	1	NM_005862.3	ENSP00000372689.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461342 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726986

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T;.;T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	1.0	D;D;D
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.33	T;T;T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	0.81	L;.;.
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-2.6	D;D;D
REVEL	Benign	0.16
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.018	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.70
MutPred		0.31		Loss of phosphorylation at S1227 (P = 0.0725);.;.;
MVP		0.26
MPC		1.9
ClinPred		0.95	D
GERP RS		5.8
Varity_R		0.39
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-136057277; COSMIC: COSV52608813; COSMIC: COSV52608813;