7-100182660-G-A

Position:

• chr7-100182660-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001282717.2(STAG3):​c.220-63G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 1,573,942 control chromosomes in the GnomAD database, including 35,532 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2710 hom., cov: 32)
  • Exomes 𝑓: 0.21 (32822 hom.)
• Consequence: STAG3 NM_001282717.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.534

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 7-100182660-G-A is Benign according to our data. Variant chr7-100182660-G-A is described in ClinVar as [Benign]. Clinvar id is 1280663.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAG3	NM_001282717.2	c.220-63G>A		intron_variant		ENST00000615138.5	NP_001269646.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAG3	ENST00000615138.5	c.220-63G>A		intron_variant		1	NM_001282717.2	ENSP00000477973.1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25357 AN: 151996 Hom.: 2704 Cov.: 32

Gnomad AFR AF: 0.0566

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.0594

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.193

GnomAD4 exome AF: 0.208 AC: 295659 AN: 1421828 Hom.: 32822 AF XY: 0.209 AC XY: 148430 AN XY: 709558

Gnomad4 AFR exome AF: 0.0513

Gnomad4 AMR exome AF: 0.110

Gnomad4 ASJ exome AF: 0.351

Gnomad4 EAS exome AF: 0.0594

Gnomad4 SAS exome AF: 0.168

Gnomad4 FIN exome AF: 0.230

Gnomad4 NFE exome AF: 0.219

Gnomad4 OTH exome AF: 0.215

GnomAD4 genome AF: 0.167 AC: 25362 AN: 152114 Hom.: 2710 Cov.: 32 AF XY: 0.167 AC XY: 12381 AN XY: 74356

Gnomad4 AFR AF: 0.0566

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.0595

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.191

Alfa AF: 0.187 Hom.: 369

Bravo AF: 0.157

Asia WGS AF: 0.0960 AC: 335 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 16, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.6
DANN	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs2056726; hg19: chr7-99780283;