rs1637001

Variant names:

• chr7-100210528-G-A
• rs1637001
• NM_001282717.2:c.3239-483G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000615138.5(STAG3):​c.3239-483G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 151,836 control chromosomes in the GnomAD database, including 38,597 homozygotes. 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: 𝑓 0.71 (38597 hom., cov: 30)
• Consequence: STAG3 ENST00000615138.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940
• Publications: 20 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000615138.5. 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.3239-483G>A		intron	N/A	NP_001269646.1
	CASTOR3P	NR_028038.2		n.2440C>T		non_coding_transcript_exon	Exon 7 of 7
	STAG3	NM_001375438.1		c.3239-483G>A		intron	N/A	NP_001362367.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAG3	ENST00000615138.5	TSL:1 MANE Select	c.3239-483G>A		intron	N/A	ENSP00000477973.1
	STAG3	ENST00000317296.9	TSL:1	c.3239-483G>A		intron	N/A	ENSP00000319318.5
	STAG3	ENST00000426455.5	TSL:1	c.3239-483G>A		intron	N/A	ENSP00000400359.1

Frequencies

GnomAD3 genomes AF: 0.707 AC: 107271 AN: 151718 Hom.: 38570 Cov.: 30

Gnomad AFR AF: 0.731

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.816

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.739

Gnomad OTH AF: 0.724

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.707 AC: 107339 AN: 151836 Hom.: 38597 Cov.: 30 AF XY: 0.702 AC XY: 52130 AN XY: 74220

African (AFR) AF: 0.731 AC: 30231 AN: 41348

American (AMR) AF: 0.559 AC: 8522 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.816 AC: 2833 AN: 3470

East Asian (EAS) AF: 0.382 AC: 1962 AN: 5140

South Asian (SAS) AF: 0.731 AC: 3521 AN: 4816

European-Finnish (FIN) AF: 0.723 AC: 7623 AN: 10540

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.739 AC: 50207 AN: 67970

Other (OTH) AF: 0.723 AC: 1525 AN: 2108

Alfa AF: 0.727 Hom.: 101451

Bravo AF: 0.693

Asia WGS AF: 0.574 AC: 1992 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.1
DANN	Benign	0.40
PhyloP100		0.094
Mutation Taster		=100/0	polymorphism (auto)

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: rs1637001; hg19: chr7-99808151;