rs200157936

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

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

Scores

1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0780
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-AS1 (HGNC:41081): (SGO1 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
SGO1NM_001199251.3 linkc.1178C>T p.Thr393Met missense_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
SGO1ENST00000412997.6 linkc.1178C>T p.Thr393Met missense_variant Exon 6 of 8 1 NM_001199251.3 ENSP00000410458.1 Q5FBB7-6

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
show subpopulations
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
show subpopulations
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs200157936; hg19: chr3-20215845; API