rs200157936

Variant names:

• chr3-20174353-G-A
• rs200157936
• NM_001199251.3:c.1178C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-20174353-G-A
• chr3-20174353-G-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001199251.3(SGO1):​c.1178C>T​(p.Thr393Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,461,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: SGO1 NM_001199251.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10087249).
• BS2: High AC in GnomAdExome4 at 24 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGO1	NM_001199251.3	c.1178C>T	p.Thr393Met	missense_variant	Exon 6 of 8	ENST00000412997.6	NP_001186180.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGO1	ENST00000412997.6	c.1178C>T	p.Thr393Met	missense_variant	Exon 6 of 8	1	NM_001199251.3	ENSP00000410458.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000318 AC: 8 AN: 251454 Hom.: 0 AF XY: 0.0000368 AC XY: 5 AN XY: 135892

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000164 AC: 24 AN: 1461852 Hom.: 0 Cov.: 32 AF XY: 0.0000165 AC XY: 12 AN XY: 727226

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000894

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: 0.0000153

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T;T;.
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.55	.;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.054
Sift	Benign	0.093	T;T;T
Sift4G	Benign	0.12	T;T;T
Polyphen		0.99	D;D;.
Vest4		0.099
MutPred		0.17		Gain of catalytic residue at T393 (P = 0.0146);Gain of catalytic residue at T393 (P = 0.0146);Gain of catalytic residue at T393 (P = 0.0146);
MVP		0.15
MPC		0.025
ClinPred		0.084	T
GERP RS		-0.57
Varity_R		0.013
gMVP		0.12

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: rs200157936; hg19: chr3-20215845;