7-100181901-CAAAAAAAAA-CAAAAAAAAAAA

Variant names:

• chr7-100181901-C-CAA
• rs3041317
• NM_001282717.2:c.117-172_117-171dupAA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001282717.2(STAG3):​c.117-172_117-171dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 69,916 control chromosomes in the GnomAD database, including 1,837 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.26 (1837 hom., cov: 25)
• Consequence: STAG3 NM_001282717.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.471
• Publications: 1 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]

STAG3 Gene-Disease associations (from GenCC):

• premature ovarian failure 8

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
• spermatogenic failure 61

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 7-100181901-C-CAA is Benign according to our data. Variant chr7-100181901-C-CAA is described in ClinVar as Benign. ClinVar VariationId is 1254489.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAG3	NM_001282717.2	MANE Select	c.117-172_117-171dupAA		intron	N/A	NP_001269646.1	D6W5U7
	STAG3	NM_001375438.1		c.117-172_117-171dupAA		intron	N/A	NP_001362367.1	D6W5U7
	STAG3	NM_001282716.1		c.117-172_117-171dupAA		intron	N/A	NP_001269645.1	Q9UJ98-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAG3	ENST00000615138.5	TSL:1 MANE Select	c.117-189_117-188insAA		intron	N/A	ENSP00000477973.1	D6W5U7
	STAG3	ENST00000317296.9	TSL:1	c.117-189_117-188insAA		intron	N/A	ENSP00000319318.5	Q9UJ98-1
	STAG3	ENST00000426455.5	TSL:1	c.117-189_117-188insAA		intron	N/A	ENSP00000400359.1	Q9UJ98-1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 18520 AN: 69938 Hom.: 1837 Cov.: 25

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.265 AC: 18509 AN: 69916 Hom.: 1837 Cov.: 25 AF XY: 0.261 AC XY: 8482 AN XY: 32466

African (AFR) AF: 0.104 AC: 1579 AN: 15122

American (AMR) AF: 0.216 AC: 1307 AN: 6060

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1078 AN: 2318

East Asian (EAS) AF: 0.119 AC: 225 AN: 1898

South Asian (SAS) AF: 0.237 AC: 473 AN: 1994

European-Finnish (FIN) AF: 0.258 AC: 854 AN: 3304

Middle Eastern (MID) AF: 0.410 AC: 59 AN: 144

European-Non Finnish (NFE) AF: 0.331 AC: 12428 AN: 37588

Other (OTH) AF: 0.290 AC: 275 AN: 948

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.47
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3041317; hg19: chr7-99779524;