chr3-20174566-T-G

Position:

chr3-20174566-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001199251.3(SGO1):c.965A>C(p.Gln322Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00342 in 1,605,192 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.014 ( 58 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 48 hom. )

Consequence

SGO1
NM_001199251.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.133

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029596388).

BP6

Variant 3-20174566-T-G is Benign according to our data. Variant chr3-20174566-T-G is described in ClinVar as [Benign]. Clinvar id is 791914.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0144 (2195/152278) while in subpopulation AFR AF= 0.0473 (1966/41544). AF 95% confidence interval is 0.0456. There are 58 homozygotes in gnomad4. There are 1035 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2195 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGO1	NM_001199251.3 linkuse as main transcript	c.965A>C	p.Gln322Pro	missense_variant	6/8	ENST00000412997.6
SGO1-AS1	NR_132785.1 linkuse as main transcript	n.240+41T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGO1	ENST00000412997.6 linkuse as main transcript	c.965A>C	p.Gln322Pro	missense_variant	6/8	1	NM_001199251.3	P2	Q5FBB7-6

Frequencies

GnomAD3 genomes

AF:

0.0144

AC:

2185

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0472

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00792

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00104

Gnomad OTH

AF:

0.0101

GnomAD3 exomes

AF:

0.00440

AC:

1055

AN:

239928

Hom.:

AF XY:

0.00342

AC XY:

443

AN XY:

129526

show subpopulations

Gnomad AFR exome

AF:

0.0482

Gnomad AMR exome

AF:

0.00368

Gnomad ASJ exome

AF:

0.00176

Gnomad EAS exome

AF:

0.000337

Gnomad SAS exome

AF:

0.000398

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00106

Gnomad OTH exome

AF:

0.00206

GnomAD4 exome

AF:

0.00227

AC:

3294

AN:

1452914

Hom.:

Cov.:

AF XY:

0.00196

AC XY:

1414

AN XY:

722184

show subpopulations

Gnomad4 AFR exome

AF:

0.0483

Gnomad4 AMR exome

AF:

0.00374

Gnomad4 ASJ exome

AF:

0.00193

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.000396

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.00105

Gnomad4 OTH exome

AF:

0.00460

GnomAD4 genome

AF:

0.0144

AC:

2195

AN:

152278

Hom.:

Cov.:

AF XY:

0.0139

AC XY:

1035

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0473

Gnomad4 AMR

AF:

0.00791

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00104

Gnomad4 OTH

AF:

0.00996

Alfa

AF:

0.00602

Hom.:

Bravo

AF:

0.0169

ESP6500AA

AF:

0.0241

AC:

106

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00498

AC:

604

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

SGO1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 16, 2019

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

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.14

DANN

Benign

0.52

DEOGEN2

Benign

0.0069

T;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.061

MetaRNN

Benign

0.0030

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

0.11

N;N;N

REVEL

Benign

0.049

Sift

Benign

0.16

T;T;T

Sift4G

Benign

0.097

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.075

MVP

0.067

MPC

0.022

ClinPred

0.0026

GERP RS

-1.5

Varity_R

0.051

gMVP

0.084

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