2-202217519-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003352.8(SUMO1):c.87+2513A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 151,772 control chromosomes in the GnomAD database, including 6,133 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 0.27 (6133 hom., cov: 30)
• Consequence: SUMO1 NM_003352.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.820

Genes affected

SUMO1 (HGNC:12502): (small ubiquitin like modifier 1) This gene encodes a protein that is a member of the SUMO (small ubiquitin-like modifier) protein family. It functions in a manner similar to ubiquitin in that it is bound to target proteins as part of a post-translational modification system. However, unlike ubiquitin which targets proteins for degradation, this protein is involved in a variety of cellular processes, such as nuclear transport, transcriptional regulation, apoptosis, and protein stability. It is not active until the last four amino acids of the carboxy-terminus have been cleaved off. Several pseudogenes have been reported for this gene. Alternate transcriptional splice variants encoding different isoforms have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUMO1	NM_003352.8	c.87+2513A>G		intron_variant		ENST00000392246.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUMO1	ENST00000392246.7	c.87+2513A>G		intron_variant		1	NM_003352.8	P1

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40383 AN: 151654 Hom.: 6131 Cov.: 30

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.266 AC: 40376 AN: 151772 Hom.: 6133 Cov.: 30 AF XY: 0.267 AC XY: 19813 AN XY: 74154

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.295

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.292

Alfa AF: 0.209 Hom.: 601

Bravo AF: 0.252

Asia WGS AF: 0.326 AC: 1133 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.93
Dann	Benign	0.63

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: rs10185956; hg19: chr2-203082242;