7-100180880-GTTTTT-GTTTTTT

Variant names:

• chr7-100180880-G-GT
• rs35965210
• NM_001282717.2:c.116+225dupT

Variant summary

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

The NM_001282717.2(STAG3):​c.116+225dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 221,346 control chromosomes in the GnomAD database, including 2,137 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2126 hom., cov: 27)
  • Exomes 𝑓: 0.26 (11 hom.)
• Consequence: STAG3 NM_001282717.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0530
• Publications: 0 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)
• spermatogenic failure 61

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP6: Variant 7-100180880-G-GT is Benign according to our data. Variant chr7-100180880-G-GT is described in ClinVar as Benign. ClinVar VariationId is 1269361.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.204 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.116+225dupT		intron	N/A	NP_001269646.1	D6W5U7
	STAG3	NM_001375438.1		c.116+225dupT		intron	N/A	NP_001362367.1	D6W5U7
	STAG3	NM_001282716.1		c.116+225dupT		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.116+201_116+202insT		intron	N/A	ENSP00000477973.1	D6W5U7
	STAG3	ENST00000317296.9	TSL:1	c.116+201_116+202insT		intron	N/A	ENSP00000319318.5	Q9UJ98-1
	STAG3	ENST00000426455.5	TSL:1	c.116+201_116+202insT		intron	N/A	ENSP00000400359.1	Q9UJ98-1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 21541 AN: 136750 Hom.: 2126 Cov.: 27

Gnomad AFR AF: 0.0649

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.0613

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.256 AC: 21686 AN: 84594 Hom.: 11 Cov.: 0 AF XY: 0.259 AC XY: 11923 AN XY: 46020

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.241 AC: 468 AN: 1942

American (AMR) AF: 0.252 AC: 785 AN: 3118

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 598 AN: 2106

East Asian (EAS) AF: 0.237 AC: 1159 AN: 4894

South Asian (SAS) AF: 0.264 AC: 3016 AN: 11444

European-Finnish (FIN) AF: 0.260 AC: 1352 AN: 5198

Middle Eastern (MID) AF: 0.296 AC: 81 AN: 274

European-Non Finnish (NFE) AF: 0.257 AC: 13008 AN: 50680

Other (OTH) AF: 0.247 AC: 1219 AN: 4938

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.157 AC: 21531 AN: 136752 Hom.: 2126 Cov.: 27 AF XY: 0.155 AC XY: 10153 AN XY: 65560

African (AFR) AF: 0.0648 AC: 2425 AN: 37416

American (AMR) AF: 0.134 AC: 1803 AN: 13452

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1174 AN: 3282

East Asian (EAS) AF: 0.0615 AC: 291 AN: 4728

South Asian (SAS) AF: 0.148 AC: 631 AN: 4274

European-Finnish (FIN) AF: 0.198 AC: 1480 AN: 7484

Middle Eastern (MID) AF: 0.310 AC: 78 AN: 252

European-Non Finnish (NFE) AF: 0.207 AC: 13063 AN: 63136

Other (OTH) AF: 0.185 AC: 344 AN: 1860

Alfa AF: 0.0435 Hom.: 77

ClinVar

ClinVar submissions as Germline

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		-0.053
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: rs35965210; hg19: chr7-99778503;