2-202236436-G-A

Variant names:

• chr2-202236436-G-A
• rs12470401
• NM_003352.8:c.12+2004C>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.12+2004C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0945 in 152,158 control chromosomes in the GnomAD database, including 915 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 0.095 (915 hom., cov: 33)
• Consequence: SUMO1 NM_003352.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.892
• Publications: 7 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=-0.66).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUMO1	NM_003352.8	c.12+2004C>T		intron_variant	Intron 1 of 4	ENST00000392246.7	NP_003343.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUMO1	ENST00000392246.7	c.12+2004C>T		intron_variant	Intron 1 of 4	1	NM_003352.8	ENSP00000376077.2
SUMO1	ENST00000409498.6	c.-199+2004C>T		intron_variant	Intron 1 of 5	3		ENSP00000386472.2

Frequencies

GnomAD3 genomes AF: 0.0947 AC: 14395 AN: 152040 Hom.: 917 Cov.: 33

Gnomad AFR AF: 0.0221

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.0697

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.0945 AC: 14382 AN: 152158 Hom.: 915 Cov.: 33 AF XY: 0.0970 AC XY: 7216 AN XY: 74394

African (AFR) AF: 0.0220 AC: 913 AN: 41526

American (AMR) AF: 0.134 AC: 2046 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0697 AC: 242 AN: 3472

East Asian (EAS) AF: 0.114 AC: 592 AN: 5184

South Asian (SAS) AF: 0.237 AC: 1141 AN: 4824

European-Finnish (FIN) AF: 0.116 AC: 1226 AN: 10574

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7856 AN: 68000

Other (OTH) AF: 0.120 AC: 254 AN: 2110

Alfa AF: 0.0661 Hom.: 87

Bravo AF: 0.0912

Asia WGS AF: 0.210 AC: 728 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.88
PhyloP100		0.89
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: rs12470401; hg19: chr2-203101159;