chr2-202237675-C-T

Variant names:

• chr2-202237675-C-T
• rs6761131
• NM_003352.8:c.12+765G>A

Variant summary

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

The NM_003352.8(SUMO1):​c.12+765G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.879 in 152,284 control chromosomes in the GnomAD database, including 58,880 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 0.88 (58880 hom., cov: 34)
• Consequence: SUMO1 NM_003352.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 5 publications found

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]

SUMO1 Gene-Disease associations (from GenCC):

• orofacial cleft 10

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003352.8. 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
	SUMO1	NM_003352.8	MANE Select	c.12+765G>A		intron	N/A	NP_003343.1	P63165-1
	SUMO1	NM_001371394.1		c.12+765G>A		intron	N/A	NP_001358323.1	B8ZZN6
	SUMO1	NM_001005781.2		c.12+765G>A		intron	N/A	NP_001005781.1	P63165-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUMO1	ENST00000392246.7	TSL:1 MANE Select	c.12+765G>A		intron	N/A	ENSP00000376077.2	P63165-1
	SUMO1	ENST00000409498.6	TSL:3	c.-199+765G>A		intron	N/A	ENSP00000386472.2	B8ZZ67
	SUMO1	ENST00000409368.5	TSL:4	c.12+765G>A		intron	N/A	ENSP00000387204.1	B8ZZN6

Frequencies

GnomAD3 genomes AF: 0.879 AC: 133689 AN: 152166 Hom.: 58825 Cov.: 34

Gnomad AFR AF: 0.887

Gnomad AMI AF: 0.927

Gnomad AMR AF: 0.857

Gnomad ASJ AF: 0.922

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.883

Gnomad OTH AF: 0.861

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

GnomAD4 genome AF: 0.879 AC: 133803 AN: 152284 Hom.: 58880 Cov.: 34 AF XY: 0.877 AC XY: 65314 AN XY: 74468

African (AFR) AF: 0.886 AC: 36821 AN: 41540

American (AMR) AF: 0.857 AC: 13116 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.922 AC: 3200 AN: 3472

East Asian (EAS) AF: 0.886 AC: 4594 AN: 5186

South Asian (SAS) AF: 0.764 AC: 3687 AN: 4826

European-Finnish (FIN) AF: 0.884 AC: 9376 AN: 10608

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.883 AC: 60096 AN: 68036

Other (OTH) AF: 0.862 AC: 1822 AN: 2114

Alfa AF: 0.879 Hom.: 7310

Bravo AF: 0.878

Asia WGS AF: 0.783 AC: 2726 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.3
DANN	Benign	0.29
PhyloP100		0.0
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: rs6761131; hg19: chr2-203102398;