NM_003352.8:c.87+1090C>T

Variant names:

• chr2-202218942-G-A
• rs7580433
• NM_003352.8:c.87+1090C>T

Variant summary

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

The NM_003352.8(SUMO1):​c.87+1090C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0569 in 151,946 control chromosomes in the GnomAD database, including 332 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 0.057 (332 hom., cov: 32)
• Consequence: SUMO1 NM_003352.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.288
• Publications: 4 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0917 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUMO1	NM_003352.8	MANE Select	c.87+1090C>T		intron	N/A	NP_003343.1
	SUMO1	NM_001371394.1		c.87+1090C>T		intron	N/A	NP_001358323.1
	SUMO1	NM_001005781.2		c.87+1090C>T		intron	N/A	NP_001005781.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUMO1	ENST00000392246.7	TSL:1 MANE Select	c.87+1090C>T		intron	N/A	ENSP00000376077.2
	SUMO1	ENST00000409498.6	TSL:3	c.-31+1090C>T		intron	N/A	ENSP00000386472.2
	SUMO1	ENST00000409368.5	TSL:4	c.87+1090C>T		intron	N/A	ENSP00000387204.1

Frequencies

GnomAD3 genomes AF: 0.0570 AC: 8661 AN: 151828 Hom.: 335 Cov.: 32

Gnomad AFR AF: 0.0170

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0596

Gnomad ASJ AF: 0.0922

Gnomad EAS AF: 0.0723

Gnomad SAS AF: 0.0993

Gnomad FIN AF: 0.0339

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0782

Gnomad OTH AF: 0.0596

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

GnomAD4 genome AF: 0.0569 AC: 8647 AN: 151946 Hom.: 332 Cov.: 32 AF XY: 0.0555 AC XY: 4122 AN XY: 74224

African (AFR) AF: 0.0170 AC: 703 AN: 41432

American (AMR) AF: 0.0595 AC: 906 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.0922 AC: 320 AN: 3472

East Asian (EAS) AF: 0.0720 AC: 372 AN: 5164

South Asian (SAS) AF: 0.0990 AC: 477 AN: 4818

European-Finnish (FIN) AF: 0.0339 AC: 357 AN: 10532

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0782 AC: 5318 AN: 67982

Other (OTH) AF: 0.0575 AC: 121 AN: 2104

Alfa AF: 0.0686 Hom.: 77

Bravo AF: 0.0562

Asia WGS AF: 0.0550 AC: 194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.47
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7580433; hg19: chr2-203083665;