chr3-20174877-C-T

Variant names:

• chr3-20174877-C-T
• rs35175566
• NM_001199251.3:c.654G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_001199251.3(SGO1):​c.654G>A​(p.Gly218Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000562 in 1,614,014 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0028 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00032 (1 hom.)
• Consequence: SGO1 NM_001199251.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.299
• Publications: 1 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 3-20174877-C-T is Benign according to our data. Variant chr3-20174877-C-T is described in ClinVar as Benign. ClinVar VariationId is 714173.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.299 with no splicing effect.

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.654G>A	p.Gly218Gly	synonymous	Exon 6 of 8	NP_001186180.1	Q5FBB7-6
	SGO1	NM_001012410.5		c.654G>A	p.Gly218Gly	synonymous	Exon 6 of 9	NP_001012410.1	Q5FBB7-1
	SGO1	NM_001199252.3		c.654G>A	p.Gly218Gly	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.654G>A	p.Gly218Gly	synonymous	Exon 6 of 8	ENSP00000410458.1	Q5FBB7-6
	SGO1	ENST00000263753.8	TSL:1	c.654G>A	p.Gly218Gly	synonymous	Exon 6 of 9	ENSP00000263753.4	Q5FBB7-1
	SGO1	ENST00000421451.5	TSL:1	c.654G>A	p.Gly218Gly	synonymous	Exon 6 of 9	ENSP00000414129.1	Q5FBB7-1

Frequencies

GnomAD3 genomes AF: 0.00283 AC: 431 AN: 152160 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00985

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000786

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.000693 AC: 174 AN: 251194 AF XY: 0.000398

Gnomad AFR exome AF: 0.00978

Gnomad AMR exome AF: 0.000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000925

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000325 AC: 475 AN: 1461736 Hom.: 1 Cov.: 32 AF XY: 0.000281 AC XY: 204 AN XY: 727146

African (AFR) AF: 0.0112 AC: 376 AN: 33476

American (AMR) AF: 0.000358 AC: 16 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86232

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53400

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.0000369 AC: 41 AN: 1111958

Other (OTH) AF: 0.000580 AC: 35 AN: 60388

GnomAD4 genome AF: 0.00284 AC: 432 AN: 152278 Hom.: 1 Cov.: 32 AF XY: 0.00270 AC XY: 201 AN XY: 74450

African (AFR) AF: 0.00984 AC: 409 AN: 41556

American (AMR) AF: 0.000785 AC: 12 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68018

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.00141 Hom.: 0

Bravo AF: 0.00329

Asia WGS AF: 0.000578 AC: 2 AN: 3476

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.4
DANN	Benign	0.67
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs35175566; hg19: chr3-20216369;