3-20179220-G-T

Variant names:

• chr3-20179220-G-T
• rs6767049
• NM_001199251.3:c.340-873C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001199251.3(SGO1):​c.340-873C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 151,982 control chromosomes in the GnomAD database, including 31,777 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.62 (31777 hom., cov: 31)
• Consequence: SGO1 NM_001199251.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.228
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.933 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.340-873C>A		intron	N/A	NP_001186180.1	Q5FBB7-6
	SGO1	NM_001012410.5		c.340-873C>A		intron	N/A	NP_001012410.1	Q5FBB7-1
	SGO1	NM_001199252.3		c.340-873C>A		intron	N/A	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.340-873C>A		intron	N/A	ENSP00000410458.1	Q5FBB7-6
	SGO1	ENST00000263753.8	TSL:1	c.340-873C>A		intron	N/A	ENSP00000263753.4	Q5FBB7-1
	SGO1	ENST00000421451.5	TSL:1	c.340-873C>A		intron	N/A	ENSP00000414129.1	Q5FBB7-1

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93916 AN: 151864 Hom.: 31711 Cov.: 31

Gnomad AFR AF: 0.862

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.955

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.565

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.619 AC: 94042 AN: 151982 Hom.: 31777 Cov.: 31 AF XY: 0.624 AC XY: 46300 AN XY: 74252

African (AFR) AF: 0.862 AC: 35746 AN: 41476

American (AMR) AF: 0.652 AC: 9959 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1070 AN: 3468

East Asian (EAS) AF: 0.955 AC: 4934 AN: 5166

South Asian (SAS) AF: 0.659 AC: 3168 AN: 4804

European-Finnish (FIN) AF: 0.539 AC: 5680 AN: 10544

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.467 AC: 31752 AN: 67934

Other (OTH) AF: 0.569 AC: 1199 AN: 2106

Alfa AF: 0.520 Hom.: 64761

Bravo AF: 0.640

Asia WGS AF: 0.794 AC: 2760 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.1
DANN	Benign	0.50
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism (auto)

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: rs6767049; hg19: chr3-20220712; COSMIC: COSV55425489;