3-20183998-G-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001199251.3(SGO1):c.30C>A(p.Ser10=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000872 in 1,588,918 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00073 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00089 (26 hom.)
• Consequence: SGO1 NM_001199251.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.105

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

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 3-20183998-G-T is Benign according to our data. Variant chr3-20183998-G-T is described in ClinVar as [Benign]. Clinvar id is 760207.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.105 with no splicing effect.
• BS2: High AC in GnomAd at 111 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGO1	NM_001199251.3	c.30C>A	p.Ser10=	synonymous_variant	2/8	ENST00000412997.6
SGO1-AS1	NR_132785.1	n.359-1977G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGO1	ENST00000412997.6	c.30C>A	p.Ser10=	synonymous_variant	2/8	1	NM_001199251.3	P2

Frequencies

GnomAD3 genomes AF: 0.000730 AC: 111 AN: 152064 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000580

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0178

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00171 AC: 389 AN: 226852 Hom.: 5 AF XY: 0.00245 AC XY: 301 AN XY: 122910

Gnomad AFR exome AF: 0.000834

Gnomad AMR exome AF: 0.0000370

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0149

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000373

Gnomad OTH exome AF: 0.000360

GnomAD4 exome AF: 0.000887 AC: 1275 AN: 1436736 Hom.: 26 Cov.: 31 AF XY: 0.00133 AC XY: 952 AN XY: 713640

Gnomad4 AFR exome AF: 0.000750

Gnomad4 AMR exome AF: 0.0000264

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0146

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000290

Gnomad4 OTH exome AF: 0.000706

GnomAD4 genome AF: 0.000729 AC: 111 AN: 152182 Hom.: 1 Cov.: 33 AF XY: 0.00102 AC XY: 76 AN XY: 74400

Gnomad4 AFR AF: 0.000578

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0178

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000132 Hom.: 0

Bravo AF: 0.000264

Asia WGS AF: 0.00434 AC: 15 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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

May 28, 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
BayesDel_noAF	Benign	-0.51
Cadd	Benign	7.6
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)		0.0		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

Other links and lift over

dbSNP: rs143768051; hg19: chr3-20225490; COSMIC: COSV55422874; COSMIC: COSV55422874;