NM_001282717.2:c.106A>C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001282717.2(STAG3):c.106A>C(p.Thr36Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,591,102 control chromosomes in the GnomAD database, including 35,127 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2727 hom., cov: 31)

Exomes 𝑓: 0.21 ( 32400 hom. )

Consequence

STAG3
NM_001282717.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.16

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005283296).

BP6

Variant 7-100180662-A-C is Benign according to our data. Variant chr7-100180662-A-C is described in ClinVar as [Benign]. Clinvar id is 1183740.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 rank	MANE	Protein	UniProt
STAG3	NM_001282717.2 link	c.106A>C	p.Thr36Pro	missense_variant	Exon 2 of 34	ENST00000615138.5	NP_001269646.1	Q9UJ98D6W5U7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAG3	ENST00000615138.5 link	c.106A>C	p.Thr36Pro	missense_variant	Exon 2 of 34	1	NM_001282717.2	ENSP00000477973.1		D6W5U7

Frequencies

GnomAD3 genomes

AF:

0.171

AC:

25904

AN:

151816

Hom.:

2722

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0691

Gnomad AMI

AF:

0.307

Gnomad AMR

AF:

0.141

Gnomad ASJ

AF:

0.366

Gnomad EAS

AF:

0.0602

Gnomad SAS

AF:

0.156

Gnomad FIN

AF:

0.234

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.225

Gnomad OTH

AF:

0.195

GnomAD3 exomes

AF:

0.182

AC:

45858

AN:

251314

Hom.:

4985

AF XY:

0.189

AC XY:

25686

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.0645

Gnomad AMR exome

AF:

0.104

Gnomad ASJ exome

AF:

0.357

Gnomad EAS exome

AF:

0.0596

Gnomad SAS exome

AF:

0.164

Gnomad FIN exome

AF:

0.231

Gnomad NFE exome

AF:

0.221

Gnomad OTH exome

AF:

0.218

GnomAD4 exome

AF:

0.205

AC:

295104

AN:

1439170

Hom.:

32400

Cov.:

AF XY:

0.207

AC XY:

148158

AN XY:

717158

show subpopulations

Gnomad4 AFR exome

AF:

0.0624

Gnomad4 AMR exome

AF:

0.110

Gnomad4 ASJ exome

AF:

0.350

Gnomad4 EAS exome

AF:

0.0601

Gnomad4 SAS exome

AF:

0.168

Gnomad4 FIN exome

AF:

0.230

Gnomad4 NFE exome

AF:

0.215

Gnomad4 OTH exome

AF:

0.214

GnomAD4 genome

AF:

0.171

AC:

25913

AN:

151932

Hom.:

2727

Cov.:

AF XY:

0.170

AC XY:

12639

AN XY:

74244

show subpopulations

Gnomad4 AFR

AF:

0.0692

Gnomad4 AMR

AF:

0.141

Gnomad4 ASJ

AF:

0.366

Gnomad4 EAS

AF:

0.0603

Gnomad4 SAS

AF:

0.158

Gnomad4 FIN

AF:

0.234

Gnomad4 NFE

AF:

0.225

Gnomad4 OTH

AF:

0.192

Alfa

AF:

0.213

Hom.:

1795

Bravo

AF:

0.161

TwinsUK

AF:

0.218

AC:

808

ALSPAC

AF:

0.216

AC:

831

ESP6500AA

AF:

0.0701

AC:

309

ESP6500EA

AF:

0.234

AC:

2016

ExAC

AF:

0.180

AC:

21866

Asia WGS

AF:

0.104

AC:

361

AN:

3478

EpiCase

AF:

0.232

EpiControl

AF:

0.235

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 05, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Premature ovarian failure 8

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Spermatogenic failure 61

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.17

DANN

Benign

0.93

DEOGEN2

Benign

0.069

T;.;.;T;.;T;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.32

.;.;T;T;T;T;T;T

MetaRNN

Benign

0.0053

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;L;L;.;.;L;.;.

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.71

N;N;.;.;N;N;D;N

REVEL

Benign

0.061

Sift

Benign

0.17

T;T;.;.;T;T;T;T

Sift4G

Benign

0.26

T;D;D;T;D;T;D;D

Polyphen

0.0

B;.;.;.;.;B;.;.

Vest4

0.059

MPC

0.60

ClinPred

0.0090

GERP RS

-4.8

Varity_R

0.093

gMVP

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over