NM_020654.5:c.2711G>T

Variant names:

• chr3-101330374-C-A
• rs61761868
• NM_020654.5:c.2711G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020654.5(SENP7):​c.2711G>T​(p.Arg904Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,453,256 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. R904C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SENP7 NM_020654.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.267
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06551629).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SENP7	NM_020654.5	c.2711G>T	p.Arg904Leu	missense_variant	Exon 20 of 24	ENST00000394095.7	NP_065705.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SENP7	ENST00000394095.7	c.2711G>T	p.Arg904Leu	missense_variant	Exon 20 of 24	1	NM_020654.5	ENSP00000377655.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1453256 Hom.: 0 Cov.: 27 AF XY: 0.00000138 AC XY: 1 AN XY: 723506

African (AFR) AF: 0.00 AC: 0 AN: 33232

American (AMR) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 85766

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00000271 AC: 3 AN: 1105018

Other (OTH) AF: 0.00 AC: 0 AN: 60088

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	7.7
DANN	Benign	0.88
DEOGEN2	Benign	0.0011	T;.;T;.;.;.
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.048	N
LIST_S2	Uncertain	0.86	D;D;D;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.066	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.90	N;.;.;.;.;.
PhyloP100		0.27
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.32	N;N;N;N;N;N
REVEL	Benign	0.0060
Sift	Benign	0.26	T;T;T;T;T;T
Sift4G	Benign	0.32	T;T;T;T;T;T
Polyphen		0.010	B;B;.;B;B;B
Vest4		0.36
MutPred		0.43		Gain of glycosylation at T908 (P = 0.0548);.;.;.;.;.;
MVP		0.19
MPC		1.1
ClinPred		0.13	T
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.059
gMVP		0.33
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs61761868; hg19: chr3-101049218; COSMIC: COSV58612222;