Variant 3-20175027-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001199251.3(SGO1):c.504A>T(p.Thr168Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,579,436 control chromosomes in the GnomAD database, including 32,919 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.19 ( 3110 hom., cov: 32)

Exomes 𝑓: 0.19 ( 29809 hom. )

Consequence

SGO1
NM_001199251.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0350

Variant links:

Genes affected

SGO1 (HGNC:25088): (shugoshin 1) The protein encoded by this gene is a member of the shugoshin family of proteins. This protein is thought to protect centromeric cohesin from cleavage during mitotic prophase by preventing phosphorylation of a cohesin subunit. Reduced expression of this gene leads to the premature loss of centromeric cohesion, mis-segregation of sister chromatids, and mitotic arrest. Evidence suggests that this protein also protects a small subset of cohesin found along the length of the chromosome arms during mitotic prophase. An isoform lacking exon 6 has been shown to play a role in the cohesion of centrioles (PMID: 16582621 and PMID:18331714). Mutations in this gene have been associated with Chronic Atrial and Intestinal Dysrhythmia (CAID) syndrome, characterized by the co-occurrence of Sick Sinus Syndrome (SSS) and Chronic Intestinal Pseudo-obstruction (CIPO) within the first four decades of life (PMID:25282101). Fibroblast cells from CAID patients exhibited both increased cell proliferation and higher rates of senescence. Pseudogenes of this gene have been found on chromosomes 1 and 7. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2015]

SGO1 links:

SGO1-AS1 (HGNC:41081): (SGO1 antisense RNA 1)

SGO1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 3-20175027-T-A is Benign according to our data. Variant chr3-20175027-T-A is described in ClinVar as [Benign]. Clinvar id is 3059284.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.035 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGO1	NM_001199251.3 link	c.504A>T	p.Thr168Thr	synonymous_variant	Exon 6 of 8	ENST00000412997.6	NP_001186180.1	Q5FBB7-6B5BUA4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGO1	ENST00000412997.6 link	c.504A>T	p.Thr168Thr	synonymous_variant	Exon 6 of 8	1	NM_001199251.3	ENSP00000410458.1		Q5FBB7-6

Frequencies

GnomAD3 genomes

AF:

0.190

AC:

28826

AN:

152078

Hom.:

3099

Cov.:

show subpopulations

Gnomad AFR

AF:

0.173

Gnomad AMI

AF:

0.0757

Gnomad AMR

AF:

0.256

Gnomad ASJ

AF:

0.0519

Gnomad EAS

AF:

0.384

Gnomad SAS

AF:

0.299

Gnomad FIN

AF:

0.168

Gnomad MID

AF:

0.0382

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.172

GnomAD3 exomes

AF:

0.223

AC:

51715

AN:

232406

Hom.:

6711

AF XY:

0.219

AC XY:

27489

AN XY:

125682

show subpopulations

Gnomad AFR exome

AF:

0.173

Gnomad AMR exome

AF:

0.343

Gnomad ASJ exome

AF:

0.0607

Gnomad EAS exome

AF:

0.375

Gnomad SAS exome

AF:

0.295

Gnomad FIN exome

AF:

0.176

Gnomad NFE exome

AF:

0.177

Gnomad OTH exome

AF:

0.181

GnomAD4 exome

AF:

0.195

AC:

277761

AN:

1427238

Hom.:

29809

Cov.:

AF XY:

0.196

AC XY:

138131

AN XY:

706250

show subpopulations

Gnomad4 AFR exome

AF:

0.169

Gnomad4 AMR exome

AF:

0.331

Gnomad4 ASJ exome

AF:

0.0592

Gnomad4 EAS exome

AF:

0.400

Gnomad4 SAS exome

AF:

0.294

Gnomad4 FIN exome

AF:

0.181

Gnomad4 NFE exome

AF:

0.180

Gnomad4 OTH exome

AF:

0.194

GnomAD4 genome

AF:

0.190

AC:

28855

AN:

152198

Hom.:

3110

Cov.:

AF XY:

0.192

AC XY:

14296

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.173

Gnomad4 AMR

AF:

0.256

Gnomad4 ASJ

AF:

0.0519

Gnomad4 EAS

AF:

0.384

Gnomad4 SAS

AF:

0.297

Gnomad4 FIN

AF:

0.168

Gnomad4 NFE

AF:

0.175

Gnomad4 OTH

AF:

0.179

Alfa

AF:

0.133

Hom.:

469

Bravo

AF:

0.193

Asia WGS

AF:

0.343

AC:

1187

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SGO1-related disorder

Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.0

DANN

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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