17-7563741-A-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015670.6(SENP3):c.665A>T(p.Glu222Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000129 in 1,551,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E222Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 31)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

SENP3
NM_015670.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.44

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24707285).

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.665A>T	p.Glu222Val	missense	Exon 2 of 11	NP_056485.2
	SENP3-EIF4A1	NR_037926.1		n.948A>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.665A>T	p.Glu222Val	missense	Exon 2 of 11	ENSP00000314029.8	Q9H4L4
SENP3-EIF4A1	ENST00000614237.1	TSL:2	n.455A>T		non_coding_transcript_exon	Exon 1 of 21	ENSP00000483614.1	A0A087X0R7
SENP3	ENST00000937871.1		c.665A>T	p.Glu222Val	missense	Exon 1 of 10	ENSP00000607930.1

Frequencies

GnomAD3 genomes

AF:

0.00000670

AC:

AN:

149168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000665

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:

0.00

GnomAD2 exomes

AF:

0.00000408

AC:

AN:

245130

AF XY:

0.00000746

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

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:

0.00

GnomAD4 exome

AF:

7.13e-7

AC:

AN:

1402824

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

696698

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31600

American (AMR)

AF:

0.0000234

AC:

AN:

42668

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23802

East Asian (EAS)

AF:

0.00

AC:

AN:

35958

South Asian (SAS)

AF:

0.00

AC:

AN:

85752

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47640

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5418

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1073626

Other (OTH)

AF:

0.00

AC:

AN:

56360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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:

0.00000670

AC:

AN:

149168

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

72736

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40738

American (AMR)

AF:

0.0000665

AC:

AN:

15036

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3428

East Asian (EAS)

AF:

0.00

AC:

AN:

4830

South Asian (SAS)

AF:

0.00

AC:

AN:

4550

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10036

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67272

Other (OTH)

AF:

0.00

AC:

AN:

2066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.00

Hom.:

Bravo

AF:

0.00000756

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

Benign

0.14

BayesDel_addAF

Benign

-0.037

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.022

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.76

M_CAP

Benign

0.024

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.34

PhyloP100

4.4

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.1

REVEL

Benign

0.19

Sift

Uncertain

0.0010

Sift4G

Benign

0.21

Polyphen

0.95

Vest4

0.38

MutPred

0.10

Loss of solvent accessibility (P = 0.0224)

MVP

0.39

MPC

0.31

ClinPred

0.63

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.20

gMVP

0.46

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

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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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over