17-7563485-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_015670.6(SENP3):c.409C>T(p.Leu137Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000338 in 1,492,474 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0015 ( 3 hom., cov: 31)

Exomes 𝑓: 0.00021 ( 5 hom. )

Consequence

SENP3
NM_015670.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.31

Publications

0 publications found

Variant links:

Genes affected

SENP3 (HGNC:17862): (SUMO specific peptidase 3) The reversible posttranslational modification of proteins by the addition of small ubiquitin-like SUMO proteins (see SUMO1; MIM 601912) is required for numerous biologic processes. SUMO-specific proteases, such as SENP3, are responsible for the initial processing of SUMO precursors to generate a C-terminal diglycine motif required for the conjugation reaction. They also have isopeptidase activity for the removal of SUMO from high molecular mass SUMO conjugates (Di Bacco et al., 2006 [PubMed 16738315]).[supplied by OMIM, Jun 2009]

SENP3 links:

SENP3-EIF4A1 (HGNC:49182): (SENP3-EIF4A1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring SUMO1/sentrin/SMT3 specific peptidase 3 (SENP3) and eukaryotic translation initiation factor 4A1 (EIF4A1) genes on chromosome 17. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Mar 2011]

SENP3-EIF4A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010442287).

BS2

High AC in GnomAd4 at 227 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015670.6. 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
	SENP3	NM_015670.6	MANE Select	c.409C>T	p.Leu137Phe	missense	Exon 2 of 11	NP_056485.2
	SENP3-EIF4A1	NR_037926.1		n.692C>T		non_coding_transcript_exon	Exon 2 of 22

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SENP3	ENST00000321337.12	TSL:1 MANE Select	c.409C>T	p.Leu137Phe	missense	Exon 2 of 11	ENSP00000314029.8	Q9H4L4
SENP3-EIF4A1	ENST00000614237.1	TSL:2	n.199C>T		non_coding_transcript_exon	Exon 1 of 21	ENSP00000483614.1	A0A087X0R7
SENP3	ENST00000937871.1		c.409C>T	p.Leu137Phe	missense	Exon 1 of 10	ENSP00000607930.1

Frequencies

GnomAD3 genomes

AF:

0.00153

AC:

227

AN:

148180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000245

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0150

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000486

GnomAD2 exomes

AF:

0.000924

AC:

142

AN:

153634

AF XY:

0.000769

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00568

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000460

GnomAD4 exome

AF:

0.000206

AC:

277

AN:

1344162

Hom.:

Cov.:

AF XY:

0.000193

AC XY:

128

AN XY:

663200

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29838

American (AMR)

AF:

0.00797

AC:

271

AN:

34002

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22968

East Asian (EAS)

AF:

0.00

AC:

AN:

30670

South Asian (SAS)

AF:

0.0000127

AC:

AN:

78746

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5382

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1044770

Other (OTH)

AF:

0.0000919

AC:

AN:

54384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00153

AC:

227

AN:

148312

Hom.:

Cov.:

AF XY:

0.00195

AC XY:

141

AN XY:

72388

show subpopulations

African (AFR)

AF:

0.0000245

AC:

AN:

40844

American (AMR)

AF:

0.0150

AC:

225

AN:

14996

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3420

East Asian (EAS)

AF:

0.00

AC:

AN:

4728

South Asian (SAS)

AF:

0.00

AC:

AN:

4450

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9906

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66706

Other (OTH)

AF:

0.000481

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000148

Hom.:

Bravo

AF:

0.00135

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.033

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.66

M_CAP

Benign

0.013

MetaRNN

Benign

0.010

MetaSVM

Benign

-0.71

MutationAssessor

Benign

0.69

PhyloP100

1.3

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.44

REVEL

Benign

0.058

Sift

Benign

0.038

Sift4G

Uncertain

0.039

Polyphen

0.98

Vest4

0.19

MutPred

0.21

Loss of helix (P = 0.079)

MVP

0.24

MPC

0.92

ClinPred

0.11

GERP RS

4.4

Varity_R

0.059

gMVP

0.34

Mutation Taster

=97/3

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over