3-101332000-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020654.5(SENP7):​c.2683G>A​(p.Asp895Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,613,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

SENP7
NM_020654.5 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.295
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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08498058).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SENP7NM_020654.5 linkc.2683G>A p.Asp895Asn missense_variant Exon 19 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.2683G>A p.Asp895Asn missense_variant Exon 19 of 24 1 NM_020654.5 ENSP00000377655.2 Q9BQF6-1

Frequencies

GnomAD3 genomes
AF:
0.0000789
AC:
12
AN:
152026
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000266
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000656
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
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251062
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135672
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS 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:
0.00000890
AC:
13
AN:
1461152
Hom.:
0
Cov.:
30
AF XY:
0.00000550
AC XY:
4
AN XY:
726878
show subpopulations
Gnomad4 AFR exome
AF:
0.000269
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000789
AC:
12
AN:
152144
Hom.:
0
Cov.:
32
AF XY:
0.0000807
AC XY:
6
AN XY:
74380
show subpopulations
Gnomad4 AFR
AF:
0.000265
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000644
Hom.:
0
Bravo
AF:
0.000125
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 12, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2683G>A (p.D895N) alteration is located in exon 19 (coding exon 19) of the SENP7 gene. This alteration results from a G to A substitution at nucleotide position 2683, causing the aspartic acid (D) at amino acid position 895 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.069
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
15
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0044
T;.;T;.;.;.
Eigen
Benign
-0.47
Eigen_PC
Benign
-0.45
FATHMM_MKL
Benign
0.23
N
LIST_S2
Benign
0.84
T;T;T;T;T;T
M_CAP
Benign
0.0094
T
MetaRNN
Benign
0.085
T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.9
L;.;.;.;.;.
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-1.4
N;N;N;N;N;N
REVEL
Benign
0.063
Sift
Benign
0.071
T;T;D;T;T;T
Sift4G
Uncertain
0.043
D;T;T;T;T;T
Polyphen
0.0040
B;B;.;B;B;B
Vest4
0.081
MVP
0.26
MPC
0.86
ClinPred
0.093
T
GERP RS
3.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.082
gMVP
0.47

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
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.

Other links and lift over

dbSNP: rs757905357; hg19: chr3-101050844; API