NM_020654.5:c.2222A>T

Variant names:

• chr3-101341664-T-A
• NM_020654.5:c.2222A>T

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.2222A>T​(p.His741Leu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SENP7 NM_020654.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.83
• 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=0.21330473).

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.2222A>T	p.His741Leu	missense	Exon 15 of 24	NP_065705.3
	SENP7	NM_001282802.2		c.2123A>T	p.His708Leu	missense	Exon 14 of 23	NP_001269731.1	Q9BQF6-2
	SENP7	NM_001077203.3		c.2027A>T	p.His676Leu	missense	Exon 14 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.2222A>T	p.His741Leu	missense	Exon 15 of 24	ENSP00000377655.2	Q9BQF6-1
	SENP7	ENST00000348610.3	TSL:1	c.2123A>T	p.His708Leu	missense	Exon 14 of 23	ENSP00000342159.3	Q9BQF6-2
	SENP7	ENST00000394094.6	TSL:1	c.2027A>T	p.His676Leu	missense	Exon 14 of 23	ENSP00000377654.2	J3QT09

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	0.14
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.062
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.8
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.054
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.018	D
Polyphen		0.0060	B
Vest4		0.49
MutPred		0.39		Loss of disorder (P = 0.0756)
MVP		0.10
MPC		0.17
ClinPred		0.82	D
GERP RS		3.1
Varity_R		0.40
gMVP		0.45
Mutation Taster		=92/8	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

hg19: chr3-101060508;