Variant 12-48088943-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 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

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 made for transcript

Verdict is Benign. Variant got -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. gnomad4_exome 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 gnomad4_exome. There are 3636 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High AC in GnomAd4 at 811 AD gene.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SENP1	ENST00000549518.6 link	c.238A>G	p.Ser80Gly	missense_variant	5/18	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

GnomAD3 exomes

AF:

0.00757

AC:

1559

AN:

206058

Hom.:

AF XY:

0.00771

AC XY:

855

AN XY:

110942

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 SAS exome

AF:

0.00482

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

Gnomad4 AFR exome

AF:

0.000742

Gnomad4 AMR exome

AF:

0.00182

Gnomad4 ASJ exome

AF:

0.0345

Gnomad4 EAS exome

AF:

0.0000257

Gnomad4 SAS exome

AF:

0.00447

Gnomad4 FIN exome

AF:

0.0284

Gnomad4 NFE exome

AF:

0.00350

Gnomad4 OTH exome

AF:

0.00674

GnomAD4 genome

AF:

0.00533

AC:

811

AN:

152282

Hom.:

Cov.:

AF XY:

0.00618

AC XY:

460

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.0326

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.0300

Gnomad4 NFE

AF:

0.00432

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00570

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 21, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

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;.

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over