3-20174992-G-T

Variant names:

• chr3-20174992-G-T
• NM_001199251.3:c.539C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001199251.3(SGO1):​c.539C>A​(p.Ser180Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,450,718 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: 6.9e-7 (0 hom.)
• Consequence: SGO1 NM_001199251.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.105

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1112591).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGO1	NM_001199251.3	c.539C>A	p.Ser180Tyr	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.539C>A	p.Ser180Tyr	missense_variant	Exon 6 of 8	1	NM_001199251.3	ENSP00000410458.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1450718 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 720630

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000119

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.047	T;T;.
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.70	.;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.032
Sift	Uncertain	0.019	D;D;D
Sift4G	Uncertain	0.052	T;T;T
Polyphen		0.89	P;P;.
Vest4		0.27
MutPred		0.23		Loss of disorder (P = 0.0043);Loss of disorder (P = 0.0043);Loss of disorder (P = 0.0043);
MVP		0.18
MPC		0.056
ClinPred		0.14	T
GERP RS		1.6
Varity_R		0.033
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-20216484;