Genetic Variant SUMO1:c.13-1864C>T (chr2-202221970-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003352.8(SUMO1):c.13-1864C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0949 in 152,166 control chromosomes in the GnomAD database, including 911 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 ( 911 hom., cov: 32)

Exomes 𝑓: 0.091 ( 0 hom. )

Consequence

SUMO1
NM_003352.8 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.84

Publications

4 publications found

Variant links:

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

SUMO1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.225 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SUMO1	NM_003352.8	MANE Select	c.13-1864C>T	intron	N/A	NP_003343.1
SUMO1	NM_001371394.1		c.13-1864C>T	intron	N/A	NP_001358323.1
SUMO1	NM_001005781.2		c.13-1864C>T	intron	N/A	NP_001005781.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SUMO1	ENST00000392246.7	TSL:1 MANE Select	c.13-1864C>T	intron	N/A	ENSP00000376077.2
SUMO1	ENST00000409498.6	TSL:3	c.-105-1864C>T	intron	N/A	ENSP00000386472.2
SUMO1	ENST00000469034.1	TSL:3	n.37C>T	non_coding_transcript_exon	Exon 1 of 5

Frequencies

GnomAD3 genomes

AF:

0.0950

AC:

14441

AN:

152026

Hom.:

913

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0231

Gnomad AMI

AF:

0.0735

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.0697

Gnomad EAS

AF:

0.114

Gnomad SAS

AF:

0.237

Gnomad FIN

AF:

0.116

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.116

Gnomad OTH

AF:

0.120

GnomAD4 exome

AF:

0.0909

AC:

AN:

Hom.:

Cov.:

AF XY:

0.143

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0625

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0949

AC:

14431

AN:

152144

Hom.:

911

Cov.:

AF XY:

0.0974

AC XY:

7239

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.0231

AC:

960

AN:

41518

American (AMR)

AF:

0.134

AC:

2051

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.0697

AC:

242

AN:

3472

East Asian (EAS)

AF:

0.114

AC:

590

AN:

5178

South Asian (SAS)

AF:

0.236

AC:

1137

AN:

4808

European-Finnish (FIN)

AF:

0.116

AC:

1228

AN:

10580

Middle Eastern (MID)

AF:

0.147

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.116

AC:

7859

AN:

68008

Other (OTH)

AF:

0.120

AC:

254

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

647

1293

1940

2586

3233

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

178

356

534

712

890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0935

Hom.:

286

Bravo

AF:

0.0917

Asia WGS

AF:

0.212

AC:

735

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.28

(source)

DANN

Benign

0.38

PhyloP100

-1.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over