3-101325991-C-G

Variant names:

• chr3-101325991-C-G
• rs201515137
• NM_020654.5:c.3105G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020654.5(SENP7):​c.3105G>C​(p.Glu1035Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SENP7 NM_020654.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.278
• Publications: 0 publications found

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]

ACMG classification

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=0.112199396).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SENP7	NM_020654.5	c.3105G>C	p.Glu1035Asp	missense_variant	Exon 24 of 24	ENST00000394095.7	NP_065705.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SENP7	ENST00000394095.7	c.3105G>C	p.Glu1035Asp	missense_variant	Exon 24 of 24	1	NM_020654.5	ENSP00000377655.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Benign	0.89
DEOGEN2	Benign	0.0018	T;.;T;.;.;.
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.85	T;T;T;T;T;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.11	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.22	N;.;.;.;.;.
PhyloP100		0.28
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	0.12	N;N;N;N;N;N
REVEL	Benign	0.023
Sift	Benign	0.50	T;T;T;T;T;T
Sift4G	Benign	0.83	T;T;T;T;T;T
Polyphen		0.39	B;B;.;B;B;P
Vest4		0.16
MutPred		0.46		Loss of ubiquitination at K1039 (P = 0.0578);.;.;.;.;.;
MVP		0.21
MPC		1.9
ClinPred		0.26	T
GERP RS		2.5
Varity_R		0.18
gMVP		0.38
Mutation Taster		=76/24	polymorphism

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

Other links and lift over

dbSNP: rs201515137; hg19: chr3-101044835;