rs12666107

Variant names:

• chr7-100180396-G-C
• rs12666107
• NM_001282717.2:c.-64-97G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001282717.2(STAG3):​c.-64-97G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 601,726 control chromosomes in the GnomAD database, including 27,845 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (7293 hom., cov: 31)
  • Exomes 𝑓: 0.28 (20552 hom.)
• Consequence: STAG3 NM_001282717.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.546
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 7-100180396-G-C is Benign according to our data. Variant chr7-100180396-G-C is described in ClinVar as Benign. ClinVar VariationId is 1267511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.607 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.-64-97G>C		intron	N/A	NP_001269646.1	D6W5U7
	STAG3	NM_001375438.1		c.-64-97G>C		intron	N/A	NP_001362367.1	D6W5U7
	STAG3	NM_001282716.1		c.-64-97G>C		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.-64-97G>C		intron	N/A	ENSP00000477973.1	D6W5U7
	STAG3	ENST00000317296.9	TSL:1	c.-64-97G>C		intron	N/A	ENSP00000319318.5	Q9UJ98-1
	STAG3	ENST00000426455.5	TSL:1	c.-64-97G>C		intron	N/A	ENSP00000400359.1	Q9UJ98-1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44541 AN: 151810 Hom.: 7274 Cov.: 31

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.266

GnomAD4 exome AF: 0.279 AC: 125524 AN: 449796 Hom.: 20552 AF XY: 0.273 AC XY: 65886 AN XY: 240972

African (AFR) AF: 0.312 AC: 3927 AN: 12580

American (AMR) AF: 0.505 AC: 10791 AN: 21380

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 2342 AN: 12540

East Asian (EAS) AF: 0.604 AC: 18711 AN: 30988

South Asian (SAS) AF: 0.244 AC: 11602 AN: 47578

European-Finnish (FIN) AF: 0.255 AC: 8186 AN: 32104

Middle Eastern (MID) AF: 0.141 AC: 248 AN: 1764

European-Non Finnish (NFE) AF: 0.238 AC: 63229 AN: 265734

Other (OTH) AF: 0.258 AC: 6488 AN: 25128

GnomAD4 genome AF: 0.294 AC: 44596 AN: 151930 Hom.: 7293 Cov.: 31 AF XY: 0.298 AC XY: 22137 AN XY: 74258

African (AFR) AF: 0.318 AC: 13161 AN: 41410

American (AMR) AF: 0.429 AC: 6552 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 615 AN: 3470

East Asian (EAS) AF: 0.625 AC: 3226 AN: 5160

South Asian (SAS) AF: 0.265 AC: 1272 AN: 4802

European-Finnish (FIN) AF: 0.258 AC: 2729 AN: 10558

Middle Eastern (MID) AF: 0.130 AC: 38 AN: 292

European-Non Finnish (NFE) AF: 0.239 AC: 16215 AN: 67958

Other (OTH) AF: 0.267 AC: 564 AN: 2114

Alfa AF: 0.259 Hom.: 683

Bravo AF: 0.310

Asia WGS AF: 0.429 AC: 1494 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.92
DANN	Benign	0.61
PhyloP100		-0.55
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: rs12666107; hg19: chr7-99778019; COSMIC: COSV52786712; COSMIC: COSV52786712;