7-100180604-G-T

Position:

chr7-100180604-G-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1

The NM_001282717.2(STAG3):c.48G>T(p.Leu16Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 1,608,446 control chromosomes in the GnomAD database, including 36,338 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 ( 2718 hom., cov: 32)

Exomes 𝑓: 0.21 ( 33620 hom. )

Consequence

STAG3
NM_001282717.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0610

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 -19 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), STAG3. . Gene score misZ 1.6577 (greater than the threshold 3.09). Trascript score misZ 3.2175 (greater than threshold 3.09). GenCC has associacion of gene with spermatogenic failure 61, premature ovarian failure 8.

BP4

Computational evidence support a benign effect (MetaRNN=0.004799068).

BP6

Variant 7-100180604-G-T is Benign according to our data. Variant chr7-100180604-G-T is described in ClinVar as [Benign]. Clinvar id is 1236675.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	UniProt
STAG3	NM_001282717.2 linkuse as main transcript	c.48G>T	p.Leu16Phe	missense_variant	2/34	ENST00000615138.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAG3	ENST00000615138.5 linkuse as main transcript	c.48G>T	p.Leu16Phe	missense_variant	2/34	1	NM_001282717.2	A2

Frequencies

GnomAD3 genomes

AF:

0.168

AC:

25515

AN:

152044

Hom.:

2712

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0599

Gnomad AMI

AF:

0.306

Gnomad AMR

AF:

0.141

Gnomad ASJ

AF:

0.366

Gnomad EAS

AF:

0.0607

Gnomad SAS

AF:

0.156

Gnomad FIN

AF:

0.234

Gnomad MID

AF:

0.328

Gnomad NFE

AF:

0.225

Gnomad OTH

AF:

0.193

GnomAD3 exomes

AF:

0.182

AC:

45692

AN:

251390

Hom.:

4973

AF XY:

0.189

AC XY:

25621

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.0541

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:

0.207

AC:

301841

AN:

1456284

Hom.:

33620

Cov.:

AF XY:

0.209

AC XY:

151226

AN XY:

724814

show subpopulations

Gnomad4 AFR exome

AF:

0.0543

Gnomad4 AMR exome

AF:

0.110

Gnomad4 ASJ exome

AF:

0.351

Gnomad4 EAS exome

AF:

0.0604

Gnomad4 SAS exome

AF:

0.169

Gnomad4 FIN exome

AF:

0.230

Gnomad4 NFE exome

AF:

0.218

Gnomad4 OTH exome

AF:

0.216

GnomAD4 genome

AF:

0.168

AC:

25524

AN:

152162

Hom.:

2718

Cov.:

AF XY:

0.168

AC XY:

12473

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0600

Gnomad4 AMR

AF:

0.140

Gnomad4 ASJ

AF:

0.366

Gnomad4 EAS

AF:

0.0609

Gnomad4 SAS

AF:

0.158

Gnomad4 FIN

AF:

0.234

Gnomad4 NFE

AF:

0.225

Gnomad4 OTH

AF:

0.191

Alfa

AF:

0.209

Hom.:

1608

Bravo

AF:

0.158

TwinsUK

AF:

0.218

AC:

808

ALSPAC

AF:

0.216

AC:

831

ESP6500AA

AF:

0.0633

AC:

279

ESP6500EA

AF:

0.234

AC:

2016

ExAC

AF:

0.179

AC:

21760

Asia WGS

AF:

0.103

AC:

359

AN:

3478

EpiCase

AF:

0.232

EpiControl

AF:

0.235

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Premature ovarian failure 8

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 05, 2021

- -

Spermatogenic failure 61

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.043

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

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.49

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

MetaRNN

Benign

0.0048

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

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.87

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

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.35

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

REVEL

Benign

0.014

Sift

Benign

0.11

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

Sift4G

Benign

0.20

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

Polyphen

0.0

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

Vest4

0.036

MutPred

0.17

Gain of helix (P = 0.0349);Gain of helix (P = 0.0349);Gain of helix (P = 0.0349);Gain of helix (P = 0.0349);Gain of helix (P = 0.0349);Gain of helix (P = 0.0349);Gain of helix (P = 0.0349);Gain of helix (P = 0.0349);

MPC

0.50

ClinPred

0.00084

GERP RS

-0.53

Varity_R

0.038

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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