3-101341769-G-C

Variant names:

• chr3-101341769-G-C
• rs144284089
• NM_020654.5:c.2117C>G

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.2117C>G​(p.Thr706Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,634 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. T706I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SENP7 NM_020654.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.377
• 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=0.09869507).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SENP7	NM_020654.5	c.2117C>G	p.Thr706Arg	missense_variant	Exon 15 of 24	ENST00000394095.7	NP_065705.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SENP7	ENST00000394095.7	c.2117C>G	p.Thr706Arg	missense_variant	Exon 15 of 24	1	NM_020654.5	ENSP00000377655.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1445634 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 717846

African (AFR) AF: 0.00 AC: 0 AN: 33300

American (AMR) AF: 0.00 AC: 0 AN: 44456

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25688

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39450

South Asian (SAS) AF: 0.00 AC: 0 AN: 84638

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53008

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099820

Other (OTH) AF: 0.00 AC: 0 AN: 59570

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	6.2
DANN	Benign	0.86
DEOGEN2	Benign	0.0056	T;.;T;.;.
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.086	N
LIST_S2	Benign	0.85	D;D;D;D;D
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.099	T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.8	L;.;.;.;.
PhyloP100		-0.38
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.4	N;N;N;N;N
REVEL	Benign	0.048
Sift	Uncertain	0.017	D;D;D;D;D
Sift4G	Benign	0.11	T;T;T;T;T
Polyphen		0.79	P;P;.;P;P
Vest4		0.21
MutPred		0.22		Loss of ubiquitination at K710 (P = 0.0286);.;.;.;.;
MVP		0.10
MPC		0.25
ClinPred		0.17	T
GERP RS		-2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.094
gMVP		0.25
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs144284089; hg19: chr3-101060613;