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]

SENP7 Gene-Disease associations (from GenCC):

• arthrogryposis multiplex congenita

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia

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).

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>C	p.Glu1035Asp	missense	Exon 24 of 24	NP_065705.3
	SENP7	NM_001282802.2		c.3006G>C	p.Glu1002Asp	missense	Exon 23 of 23	NP_001269731.1	Q9BQF6-2
	SENP7	NM_001077203.3		c.2910G>C	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>C	p.Glu1035Asp	missense	Exon 24 of 24	ENSP00000377655.2	Q9BQF6-1
	SENP7	ENST00000348610.3	TSL:1	c.3006G>C	p.Glu1002Asp	missense	Exon 23 of 23	ENSP00000342159.3	Q9BQF6-2
	SENP7	ENST00000394094.6	TSL:1	c.2910G>C	p.Glu970Asp	missense	Exon 23 of 23	ENSP00000377654.2	J3QT09

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
PhyloP100		0.28
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs201515137; hg19: chr3-101044835;