NM_001199251.3:c.*8G>A

Variant names:

• chr3-20170696-C-T
• rs114711704
• NM_001199251.3:c.*8G>A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_001199251.3(SGO1):​c.*8G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00185 in 1,566,434 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0094 (19 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (17 hom.)
• Consequence: SGO1 NM_001199251.3 3_prime_UTR
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.0260

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 3-20170696-C-T is Benign according to our data. Variant chr3-20170696-C-T is described in ClinVar as [Benign]. Clinvar id is 3352144.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00942 (1426/151460) while in subpopulation AFR AF= 0.032 (1322/41250). AF 95% confidence interval is 0.0306. There are 19 homozygotes in gnomad4. There are 649 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1426 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGO1	NM_001199251.3	c.*8G>A		3_prime_UTR_variant	Exon 8 of 8	ENST00000412997.6	NP_001186180.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGO1	ENST00000412997	c.*8G>A		3_prime_UTR_variant	Exon 8 of 8	1	NM_001199251.3	ENSP00000410458.1

Frequencies

GnomAD3 genomes AF: 0.00941 AC: 1424 AN: 151342 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.0321

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00368

Gnomad ASJ AF: 0.00579

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000177

Gnomad OTH AF: 0.00624

GnomAD3 exomes AF: 0.00262 AC: 541 AN: 206856 Hom.: 11 AF XY: 0.00177 AC XY: 200 AN XY: 112764

Gnomad AFR exome AF: 0.0306

Gnomad AMR exome AF: 0.00206

Gnomad ASJ exome AF: 0.00476

Gnomad EAS exome AF: 0.0000657

Gnomad SAS exome AF: 0.0000432

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000162

Gnomad OTH exome AF: 0.00243

GnomAD4 exome AF: 0.00104 AC: 1467 AN: 1414974 Hom.: 17 Cov.: 31 AF XY: 0.000883 AC XY: 621 AN XY: 703234

Gnomad4 AFR exome AF: 0.0303

Gnomad4 AMR exome AF: 0.00213

Gnomad4 ASJ exome AF: 0.00520

Gnomad4 EAS exome AF: 0.0000260

Gnomad4 SAS exome AF: 0.0000385

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000162

Gnomad4 OTH exome AF: 0.00273

GnomAD4 genome AF: 0.00942 AC: 1426 AN: 151460 Hom.: 19 Cov.: 32 AF XY: 0.00876 AC XY: 649 AN XY: 74072

Gnomad4 AFR AF: 0.0320

Gnomad4 AMR AF: 0.00368

Gnomad4 ASJ AF: 0.00579

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000177

Gnomad4 OTH AF: 0.00618

Alfa AF: 0.00486 Hom.: 3

Bravo AF: 0.0106

Asia WGS AF: 0.00173 AC: 6 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

SGO1-related disorder Benign:1

May 15, 2024

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.32
DANN	Benign	0.64

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

LitVar

Other links and lift over

dbSNP: rs114711704; hg19: chr3-20212188;