NM_001199251.3:c.504A>T

Variant names:

• chr3-20175027-T-A
• rs61729306
• NM_001199251.3:c.504A>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

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 (★).

• Frequency:
  • Genomes: 𝑓 0.19 (3110 hom., cov: 32)
  • Exomes 𝑓: 0.19 (29809 hom.)
• Consequence: SGO1 NM_001199251.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.0350
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -15 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 VariationId is 3059284.Status of the report is criteria_provided_single_submitter, 1 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199251.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGO1	NM_001199251.3	MANE Select	c.504A>T	p.Thr168Thr	synonymous	Exon 6 of 8	NP_001186180.1	Q5FBB7-6
	SGO1	NM_001012410.5		c.504A>T	p.Thr168Thr	synonymous	Exon 6 of 9	NP_001012410.1	Q5FBB7-1
	SGO1	NM_001199252.3		c.504A>T	p.Thr168Thr	synonymous	Exon 6 of 9	NP_001186181.1	Q5FBB7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGO1	ENST00000412997.6	TSL:1 MANE Select	c.504A>T	p.Thr168Thr	synonymous	Exon 6 of 8	ENSP00000410458.1	Q5FBB7-6
	SGO1	ENST00000263753.8	TSL:1	c.504A>T	p.Thr168Thr	synonymous	Exon 6 of 9	ENSP00000263753.4	Q5FBB7-1
	SGO1	ENST00000421451.5	TSL:1	c.504A>T	p.Thr168Thr	synonymous	Exon 6 of 9	ENSP00000414129.1	Q5FBB7-1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28826 AN: 152078 Hom.: 3099 Cov.: 32

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

GnomAD2 exomes AF: 0.223 AC: 51715 AN: 232406 AF XY: 0.219

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 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.: 31 AF XY: 0.196 AC XY: 138131 AN XY: 706250

African (AFR) AF: 0.169 AC: 5479 AN: 32380

American (AMR) AF: 0.331 AC: 13279 AN: 40166

Ashkenazi Jewish (ASJ) AF: 0.0592 AC: 1463 AN: 24712

East Asian (EAS) AF: 0.400 AC: 15639 AN: 39076

South Asian (SAS) AF: 0.294 AC: 23721 AN: 80752

European-Finnish (FIN) AF: 0.181 AC: 9486 AN: 52542

Middle Eastern (MID) AF: 0.0689 AC: 386 AN: 5600

European-Non Finnish (NFE) AF: 0.180 AC: 196886 AN: 1093266

Other (OTH) AF: 0.194 AC: 11422 AN: 58744

GnomAD4 genome AF: 0.190 AC: 28855 AN: 152198 Hom.: 3110 Cov.: 32 AF XY: 0.192 AC XY: 14296 AN XY: 74424

African (AFR) AF: 0.173 AC: 7176 AN: 41530

American (AMR) AF: 0.256 AC: 3915 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0519 AC: 180 AN: 3466

East Asian (EAS) AF: 0.384 AC: 1986 AN: 5178

South Asian (SAS) AF: 0.297 AC: 1436 AN: 4830

European-Finnish (FIN) AF: 0.168 AC: 1778 AN: 10588

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11927 AN: 67998

Other (OTH) AF: 0.179 AC: 378 AN: 2114

Alfa AF: 0.133 Hom.: 469

Bravo AF: 0.193

Asia WGS AF: 0.343 AC: 1187 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)
-	-	1	SGO1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.0
DANN	Benign	0.67
PhyloP100		0.035
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs61729306; hg19: chr3-20216519; COSMIC: COSV55423758; COSMIC: COSV55423758;