chr7-100204096-C-G

Variant names:

• chr7-100204096-C-G
• rs764841861
• NM_001282717.2:c.2776C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001282717.2(STAG3):​c.2776C>G​(p.Arg926Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict 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: 31)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: STAG3 NM_001282717.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71
• Publications: 3 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17158628).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAG3	NM_001282717.2	MANE Select	c.2776C>G	p.Arg926Gly	missense	Exon 26 of 34	NP_001269646.1
	STAG3	NM_001375438.1		c.2776C>G	p.Arg926Gly	missense	Exon 26 of 34	NP_001362367.1
	STAG3	NM_001282716.1		c.2776C>G	p.Arg926Gly	missense	Exon 26 of 34	NP_001269645.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAG3	ENST00000615138.5	TSL:1 MANE Select	c.2776C>G	p.Arg926Gly	missense	Exon 26 of 34	ENSP00000477973.1
	STAG3	ENST00000317296.9	TSL:1	c.2776C>G	p.Arg926Gly	missense	Exon 26 of 34	ENSP00000319318.5
	STAG3	ENST00000426455.5	TSL:1	c.2776C>G	p.Arg926Gly	missense	Exon 26 of 34	ENSP00000400359.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461736 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727184

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111976

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.46	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.7
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.077
Sift	Benign	0.045	D
Sift4G	Uncertain	0.031	D
Polyphen		0.0020	B
Vest4		0.36
MutPred		0.46		Loss of MoRF binding (P = 0.0419)
MVP		0.34
MPC		0.17
ClinPred		0.54	D
GERP RS		2.8
Varity_R		0.13
gMVP		0.42
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs764841861; hg19: chr7-99801719;