chr3-20175019-A-C

Variant names:

• chr3-20175019-A-C
• NM_001199251.3:c.512T>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001199251.3(SGO1):​c.512T>G​(p.Val171Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,433,422 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V171A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SGO1 NM_001199251.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.424

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05457139).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGO1	NM_001199251.3	c.512T>G	p.Val171Gly	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.512T>G	p.Val171Gly	missense_variant	Exon 6 of 8	1	NM_001199251.3	ENSP00000410458.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1433422 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 710200

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.12e-7

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	0.082
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	10
DANN	Benign	0.62
DEOGEN2	Benign	0.023	.;T;.;.;T;.;.;.
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.31	.;.;T;T;T;T;.;T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.055	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.69	N;N;N;N;N;N;N;N
REVEL	Benign	0.025
Sift	Benign	0.17	T;T;T;T;T;T;T;T
Sift4G	Benign	0.27	T;T;T;D;T;T;T;T
Polyphen		0.0	B;B;B;B;B;.;B;B
Vest4		0.060
MutPred		0.29		Loss of stability (P = 0.0062);Loss of stability (P = 0.0062);Loss of stability (P = 0.0062);Loss of stability (P = 0.0062);Loss of stability (P = 0.0062);Loss of stability (P = 0.0062);Loss of stability (P = 0.0062);Loss of stability (P = 0.0062);
MVP		0.11
MPC		0.022
ClinPred		0.064	T
GERP RS		0.86
Varity_R		0.047
gMVP		0.049

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-20216511;