NM_020654.5:c.2711G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020654.5(SENP7):​c.2711G>C​(p.Arg904Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00062 in 1,605,310 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R904C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00065 ( 1 hom. )

Consequence

SENP7
NM_020654.5 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.267

Publications

4 publications found
Variant links:
Genes affected
SENP7 (HGNC:30402): (SUMO specific peptidase 7) The reversible posttranslational modification of proteins by the addition of small ubiquitin-like SUMO proteins (see SUMO1; MIM 601912) is required for many cellular processes. SUMO-specific proteases, such as SENP7, process SUMO precursors to generate a C-terminal diglycine motif required for the conjugation reaction. They also display isopeptidase activity for deconjugation of SUMO-conjugated substrates (Lima and Reverter, 2008 [PubMed 18799455]).[supplied by OMIM, Jun 2009]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.02587682).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SENP7NM_020654.5 linkc.2711G>C p.Arg904Pro missense_variant Exon 20 of 24 ENST00000394095.7 NP_065705.3 Q9BQF6-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SENP7ENST00000394095.7 linkc.2711G>C p.Arg904Pro missense_variant Exon 20 of 24 1 NM_020654.5 ENSP00000377655.2 Q9BQF6-1

Frequencies

GnomAD3 genomes
AF:
0.000375
AC:
57
AN:
152086
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000966
Gnomad AMI
AF:
0.00219
Gnomad AMR
AF:
0.000196
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:
0.000706
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.000368
AC:
92
AN:
249786
AF XY:
0.000370
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000176
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000734
Gnomad OTH exome
AF:
0.000494
GnomAD4 exome
AF:
0.000645
AC:
938
AN:
1453224
Hom.:
1
Cov.:
27
AF XY:
0.000611
AC XY:
442
AN XY:
723490
show subpopulations
African (AFR)
AF:
0.0000301
AC:
1
AN:
33232
American (AMR)
AF:
0.000157
AC:
7
AN:
44482
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26026
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39530
South Asian (SAS)
AF:
0.0000117
AC:
1
AN:
85766
European-Finnish (FIN)
AF:
0.0000187
AC:
1
AN:
53370
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5744
European-Non Finnish (NFE)
AF:
0.000818
AC:
904
AN:
1104986
Other (OTH)
AF:
0.000399
AC:
24
AN:
60088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.442
Heterozygous variant carriers
0
32
64
96
128
160
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
38
76
114
152
190
<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:
0.000375
AC:
57
AN:
152086
Hom.:
0
Cov.:
32
AF XY:
0.000296
AC XY:
22
AN XY:
74278
show subpopulations
African (AFR)
AF:
0.0000966
AC:
4
AN:
41404
American (AMR)
AF:
0.000196
AC:
3
AN:
15268
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5190
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4824
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10582
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.000706
AC:
48
AN:
68028
Other (OTH)
AF:
0.00
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
2
4
7
9
11
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.000574
Hom.:
1
Bravo
AF:
0.000450
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000698
AC:
6
ExAC
AF:
0.000288
AC:
35
EpiCase
AF:
0.000932
EpiControl
AF:
0.000775

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
13
DANN
Benign
0.89
DEOGEN2
Benign
0.00055
T;.;T;.;.;.
Eigen
Benign
-0.71
Eigen_PC
Benign
-0.72
FATHMM_MKL
Benign
0.052
N
LIST_S2
Benign
0.83
T;T;T;T;T;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.026
T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.17
N;.;.;.;.;.
PhyloP100
0.27
PrimateAI
Benign
0.22
T
PROVEAN
Benign
-0.15
N;N;N;N;N;N
REVEL
Benign
0.042
Sift
Benign
0.21
T;T;T;T;T;T
Sift4G
Benign
0.27
T;T;T;T;T;T
Polyphen
0.92
P;P;.;B;P;P
Vest4
0.34
MVP
0.24
MPC
1.6
ClinPred
0.027
T
GERP RS
1.6
Varity_R
0.14
gMVP
0.44
Mutation Taster
=76/24
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs61761868; hg19: chr3-101049218; API