rs3769817

Variant names:

• chr2-202214584-T-C
• rs3769817
• NM_003352.8:c.88-150A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-202214584-T-C
• chr2-202214584-T-A
• chr2-202214584-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003352.8(SUMO1):​c.88-150A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.878 in 577,096 control chromosomes in the GnomAD database, including 222,958 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.88 (58895 hom., cov: 33)
  • Exomes 𝑓: 0.88 (164063 hom.)
• Consequence: SUMO1 NM_003352.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.119
• Publications: 11 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 2-202214584-T-C is Benign according to our data. Variant chr2-202214584-T-C is described in ClinVar as Benign. ClinVar VariationId is 1258470.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.88-150A>G		intron	N/A	NP_003343.1	P63165-1
	SUMO1	NM_001371394.1		c.88-150A>G		intron	N/A	NP_001358323.1	B8ZZN6
	SUMO1	NM_001005781.2		c.88-150A>G		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.88-150A>G		intron	N/A	ENSP00000376077.2	P63165-1
	SUMO1	ENST00000409498.6	TSL:3	c.-30-150A>G		intron	N/A	ENSP00000386472.2	B8ZZ67
	SUMO1	ENST00000409368.5	TSL:4	c.88-150A>G		intron	N/A	ENSP00000387204.1	B8ZZN6

Frequencies

GnomAD3 genomes AF: 0.879 AC: 133682 AN: 152116 Hom.: 58840 Cov.: 33

Gnomad AFR AF: 0.887

Gnomad AMI AF: 0.929

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: 0.834

Gnomad NFE AF: 0.883

Gnomad OTH AF: 0.861

GnomAD4 exome AF: 0.878 AC: 372898 AN: 424862 Hom.: 164063 AF XY: 0.873 AC XY: 198356 AN XY: 227324

African (AFR) AF: 0.885 AC: 7647 AN: 8642

American (AMR) AF: 0.864 AC: 9798 AN: 11346

Ashkenazi Jewish (ASJ) AF: 0.916 AC: 11800 AN: 12880

East Asian (EAS) AF: 0.931 AC: 22881 AN: 24564

South Asian (SAS) AF: 0.777 AC: 29260 AN: 37672

European-Finnish (FIN) AF: 0.877 AC: 32325 AN: 36856

Middle Eastern (MID) AF: 0.895 AC: 1815 AN: 2028

European-Non Finnish (NFE) AF: 0.886 AC: 236286 AN: 266734

Other (OTH) AF: 0.873 AC: 21086 AN: 24140

GnomAD4 genome AF: 0.879 AC: 133796 AN: 152234 Hom.: 58895 Cov.: 33 AF XY: 0.877 AC XY: 65294 AN XY: 74424

African (AFR) AF: 0.887 AC: 36834 AN: 41542

American (AMR) AF: 0.857 AC: 13095 AN: 15272

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

East Asian (EAS) AF: 0.886 AC: 4599 AN: 5190

South Asian (SAS) AF: 0.764 AC: 3685 AN: 4824

European-Finnish (FIN) AF: 0.884 AC: 9371 AN: 10596

Middle Eastern (MID) AF: 0.836 AC: 244 AN: 292

European-Non Finnish (NFE) AF: 0.884 AC: 60103 AN: 68024

Other (OTH) AF: 0.862 AC: 1820 AN: 2112

Alfa AF: 0.880 Hom.: 12674

Bravo AF: 0.878

Asia WGS AF: 0.784 AC: 2722 AN: 3468

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.75
PhyloP100		-0.12
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3769817; hg19: chr2-203079307;