chr7-100180662-A-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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

Publications

25 publications found

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 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)

STAG3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STAG3	NM_001282717.2	MANE Select	c.106A>C	p.Thr36Pro	missense	Exon 2 of 34	NP_001269646.1	D6W5U7
STAG3	NM_001375438.1		c.106A>C	p.Thr36Pro	missense	Exon 2 of 34	NP_001362367.1	D6W5U7
STAG3	NM_001282716.1		c.106A>C	p.Thr36Pro	missense	Exon 2 of 34	NP_001269645.1	Q9UJ98-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STAG3	ENST00000615138.5	TSL:1 MANE Select	c.106A>C	p.Thr36Pro	missense	Exon 2 of 34	ENSP00000477973.1	D6W5U7
STAG3	ENST00000317296.9	TSL:1	c.106A>C	p.Thr36Pro	missense	Exon 2 of 34	ENSP00000319318.5	Q9UJ98-1
STAG3	ENST00000426455.5	TSL:1	c.106A>C	p.Thr36Pro	missense	Exon 2 of 34	ENSP00000400359.1	Q9UJ98-1

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

GnomAD2 exomes

AF:

0.182

AC:

45858

AN:

251314

AF XY:

0.189

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 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

African (AFR)

AF:

0.0624

AC:

2075

AN:

33244

American (AMR)

AF:

0.110

AC:

4928

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.350

AC:

9080

AN:

25916

East Asian (EAS)

AF:

0.0601

AC:

2383

AN:

39624

South Asian (SAS)

AF:

0.168

AC:

14415

AN:

85838

European-Finnish (FIN)

AF:

0.230

AC:

12252

AN:

53352

Middle Eastern (MID)

AF:

0.367

AC:

2091

AN:

5700

European-Non Finnish (NFE)

AF:

0.215

AC:

235105

AN:

1091162

Other (OTH)

AF:

0.214

AC:

12775

AN:

59650

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.436

Heterozygous variant carriers

10408

20815

31223

41630

52038

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7760

15520

23280

31040

38800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.171

AC:

25913

AN:

151932

Hom.:

2727

Cov.:

AF XY:

0.170

AC XY:

12639

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.0692

AC:

2868

AN:

41428

American (AMR)

AF:

0.141

AC:

2151

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.366

AC:

1271

AN:

3468

East Asian (EAS)

AF:

0.0603

AC:

312

AN:

5172

South Asian (SAS)

AF:

0.158

AC:

758

AN:

4812

European-Finnish (FIN)

AF:

0.234

AC:

2469

AN:

10540

Middle Eastern (MID)

AF:

0.327

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.225

AC:

15303

AN:

67942

Other (OTH)

AF:

0.192

AC:

406

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1068

2136

3204

4272

5340

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

286

572

858

1144

1430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.206

Hom.:

2268

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

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Premature ovarian failure 8 (1)

Spermatogenic failure 61 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.17

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.069

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.32

MetaRNN

Benign

0.0053

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PhyloP100

-1.2

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.71

REVEL

Benign

0.061

Sift

Benign

0.17

Sift4G

Benign

0.26

Polyphen

0.0

Vest4

0.059

MPC

0.60

ClinPred

0.0090

GERP RS

-4.8

Varity_R

0.093

gMVP

0.14

Mutation Taster

=94/6

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over