Variant 3-136341454-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The ENST00000383202.7(STAG1):c.3544G>A(p.Val1182Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000103 in 1,458,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. V1182V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

STAG1
ENST00000383202.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.74

Variant links:

Genes affected

STAG1 (HGNC:11354): (STAG1 cohesin complex component) This gene is a member of the SCC3 family and is expressed in the nucleus. It encodes a component of cohesin, a multisubunit protein complex that provides sister chromatid cohesion along the length of a chromosome from DNA replication through prophase and prometaphase, after which it is dissociated in preparation for segregation during anaphase. [provided by RefSeq, Jul 2008]

STAG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), STAG1. . Gene score misZ 4.4429 (greater than the threshold 3.09). Trascript score misZ 4.1606 (greater than threshold 3.09). GenCC has associacion of gene with complex neurodevelopmental disorder, intellectual disability, autosomal dominant 47.

BP4

Computational evidence support a benign effect (MetaRNN=0.20463088).

BS2

High AC in GnomAdExome4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAG1	NM_005862.3 linkuse as main transcript	c.3544G>A	p.Val1182Met	missense_variant	31/34	ENST00000383202.7	NP_005853.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAG1	ENST00000383202.7 linkuse as main transcript	c.3544G>A	p.Val1182Met	missense_variant	31/34	1	NM_005862.3	ENSP00000372689	P1	Q8WVM7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251090

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135716

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1458184

Hom.:

Cov.:

AF XY:

0.00000827

AC XY:

AN XY:

725714

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2022

The c.3544G>A (p.V1182M) alteration is located in exon 31 (coding exon 30) of the STAG1 gene. This alteration results from a G to A substitution at nucleotide position 3544, causing the valine (V) at amino acid position 1182 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.022

T;T

Eigen

Benign

0.19

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.76

N;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.40

N;N

REVEL

Benign

0.071

Sift

Benign

0.078

T;T

Sift4G

Benign

0.30

T;T

Polyphen

0.10

B;.

Vest4

0.36

MutPred

0.35

Gain of disorder (P = 0.0253);.;

MVP

0.14

MPC

0.81

ClinPred

0.41

GERP RS

5.9

Varity_R

0.083

gMVP

0.27

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