12-48088943-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001267594.2(SENP1):c.238A>G(p.Ser80Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00505 in 1,586,598 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0053 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0050 ( 64 hom. )

Consequence

SENP1
NM_001267594.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.67

Publications

8 publications found

Variant links:

Genes affected

SENP1 (HGNC:17927): (SUMO specific peptidase 1) This gene encodes a cysteine protease that specifically targets members of the small ubiquitin-like modifier (SUMO) protein family. This protease regulates SUMO pathways by deconjugating sumoylated proteins. This protease also functions to process the precursor SUMO proteins into their mature form. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

SENP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037702918).

BP6

Variant 12-48088943-T-C is Benign according to our data. Variant chr12-48088943-T-C is described in ClinVar as [Benign]. Clinvar id is 774213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00502 (7200/1434316) while in subpopulation MID AF = 0.021 (120/5726). AF 95% confidence interval is 0.0179. There are 64 homozygotes in GnomAdExome4. There are 3636 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High AC in GnomAd4 at 811 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SENP1	NM_001267594.2 link	c.238A>G	p.Ser80Gly	missense_variant	Exon 5 of 18	ENST00000549518.6	NP_001254523.1	Q9P0U3-1Q6N001

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SENP1	ENST00000549518.6 link	c.238A>G	p.Ser80Gly	missense_variant	Exon 5 of 18	1	NM_001267594.2	ENSP00000447328.1		Q9P0U3-1

Frequencies

GnomAD3 genomes

AF:

0.00532

AC:

810

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.0326

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.0300

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00432

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00757

AC:

1559

AN:

206058

AF XY:

0.00771

show subpopulations

Gnomad AFR exome

AF:

0.000560

Gnomad AMR exome

AF:

0.00190

Gnomad ASJ exome

AF:

0.0345

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0277

Gnomad NFE exome

AF:

0.00508

Gnomad OTH exome

AF:

0.00872

GnomAD4 exome

AF:

0.00502

AC:

7200

AN:

1434316

Hom.:

Cov.:

AF XY:

0.00511

AC XY:

3636

AN XY:

711570

show subpopulations

African (AFR)

AF:

0.000742

AC:

AN:

32334

American (AMR)

AF:

0.00182

AC:

AN:

38378

Ashkenazi Jewish (ASJ)

AF:

0.0345

AC:

879

AN:

25484

East Asian (EAS)

AF:

0.0000257

AC:

AN:

38878

South Asian (SAS)

AF:

0.00447

AC:

367

AN:

82108

European-Finnish (FIN)

AF:

0.0284

AC:

1489

AN:

52412

Middle Eastern (MID)

AF:

0.0210

AC:

120

AN:

5726

European-Non Finnish (NFE)

AF:

0.00350

AC:

3849

AN:

1099480

Other (OTH)

AF:

0.00674

AC:

401

AN:

59516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

352

704

1055

1407

1759

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00533

AC:

811

AN:

152282

Hom.:

Cov.:

AF XY:

0.00618

AC XY:

460

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.000505

AC:

AN:

41564

American (AMR)

AF:

0.00235

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0326

AC:

113

AN:

3466

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.00207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0300

AC:

318

AN:

10600

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00432

AC:

294

AN:

68024

Other (OTH)

AF:

0.00284

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

124

166

207

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00520

Hom.:

Bravo

AF:

0.00345

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000277

AC:

ESP6500EA

AF:

0.00553

AC:

ExAC

AF:

0.00594

AC:

715

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 21, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

T;.;T;.

Eigen

Benign

-0.059

Eigen_PC

Benign

0.14

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.78

.;T;T;T

MetaRNN

Benign

0.0038

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

L;L;L;.

PhyloP100

4.7

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.97

N;N;N;D

REVEL

Benign

0.048

Sift

Uncertain

0.0040

D;D;D;D

Sift4G

Benign

0.20

T;T;T;.

Polyphen

0.018

B;B;B;.

Vest4

0.26

MVP

0.34

ClinPred

0.020

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.29

Mutation Taster

=99/1

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

12-48088943-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over