rs201515137

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-101325991-C-A
• chr3-101325991-C-G
• chr3-101325991-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_020654.5(SENP7):​c.3105G>T​(p.Glu1035Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000222 in 1,610,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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: 0.00024 (0 hom.)
• Consequence: SENP7 NM_020654.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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]

SENP7 Gene-Disease associations (from GenCC):

• arthrogryposis multiplex congenita

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10228565).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020654.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SENP7	NM_020654.5	MANE Select	c.3105G>T	p.Glu1035Asp	missense	Exon 24 of 24	NP_065705.3
	SENP7	NM_001282802.2		c.3006G>T	p.Glu1002Asp	missense	Exon 23 of 23	NP_001269731.1	Q9BQF6-2
	SENP7	NM_001077203.3		c.2910G>T	p.Glu970Asp	missense	Exon 23 of 23	NP_001070671.1	J3QT09

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SENP7	ENST00000394095.7	TSL:1 MANE Select	c.3105G>T	p.Glu1035Asp	missense	Exon 24 of 24	ENSP00000377655.2	Q9BQF6-1
	SENP7	ENST00000348610.3	TSL:1	c.3006G>T	p.Glu1002Asp	missense	Exon 23 of 23	ENSP00000342159.3	Q9BQF6-2
	SENP7	ENST00000394094.6	TSL:1	c.2910G>T	p.Glu970Asp	missense	Exon 23 of 23	ENSP00000377654.2	J3QT09

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152022 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000482 AC: 12 AN: 249022 AF XY: 0.0000594

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000977

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000236 AC: 345 AN: 1458884 Hom.: 0 Cov.: 30 AF XY: 0.000227 AC XY: 165 AN XY: 725710

African (AFR) AF: 0.0000601 AC: 2 AN: 33266

American (AMR) AF: 0.00 AC: 0 AN: 44400

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26032

East Asian (EAS) AF: 0.00 AC: 0 AN: 39498

South Asian (SAS) AF: 0.00 AC: 0 AN: 85964

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.000304 AC: 338 AN: 1110414

Other (OTH) AF: 0.0000830 AC: 5 AN: 60220

GnomAD4 genome AF: 0.0000789 AC: 12 AN: 152022 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74242

African (AFR) AF: 0.0000483 AC: 2 AN: 41402

American (AMR) AF: 0.00 AC: 0 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.000117 Hom.: 0

Bravo AF: 0.0000567

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Benign	0.88
DEOGEN2	Benign	0.0018	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.22	N
PhyloP100		0.28
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	0.12	N
REVEL	Benign	0.018
Sift	Benign	0.50	T
Sift4G	Benign	0.83	T
Polyphen		0.39	B
Vest4		0.16
MutPred		0.46		Loss of ubiquitination at K1039 (P = 0.0578)
MVP		0.22
MPC		1.9
ClinPred		0.37	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;