Genetic Variant NM_020654.5:c.2350T>C (chr3-101340102-A-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_020654.5(SENP7):c.2350T>C(p.Tyr784His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 13/22 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SENP7
NM_020654.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.40

Publications

0 publications found

Variant links:

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

SENP7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.859

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SENP7	NM_020654.5	MANE Select	c.2350T>C	p.Tyr784His	missense	Exon 16 of 24	NP_065705.3
SENP7	NM_001282802.2		c.2251T>C	p.Tyr751His	missense	Exon 15 of 23	NP_001269731.1	Q9BQF6-2
SENP7	NM_001077203.3		c.2155T>C	p.Tyr719His	missense	Exon 15 of 23	NP_001070671.1	J3QT09

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SENP7	ENST00000394095.7	TSL:1 MANE Select	c.2350T>C	p.Tyr784His	missense	Exon 16 of 24	ENSP00000377655.2	Q9BQF6-1
SENP7	ENST00000348610.3	TSL:1	c.2251T>C	p.Tyr751His	missense	Exon 15 of 23	ENSP00000342159.3	Q9BQF6-2
SENP7	ENST00000394094.6	TSL:1	c.2155T>C	p.Tyr719His	missense	Exon 15 of 23	ENSP00000377654.2	J3QT09

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1428872

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

710470

African (AFR)

AF:

0.00

AC:

AN:

31416

American (AMR)

AF:

0.00

AC:

AN:

34800

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24956

East Asian (EAS)

AF:

0.00

AC:

AN:

38708

South Asian (SAS)

AF:

0.00

AC:

AN:

79656

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52640

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5418

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1102264

Other (OTH)

AF:

0.00

AC:

AN:

59014

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.18

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

1.0

M_CAP

Benign

0.029

MetaRNN

Pathogenic

0.86

MetaSVM

Uncertain

-0.19

MutationAssessor

Pathogenic

3.4

PhyloP100

8.4

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-4.8

REVEL

Pathogenic

0.75

Sift

Uncertain

0.0030

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.92

MutPred

0.74

Loss of stability (P = 0.0313)

MVP

0.42

MPC

2.2

ClinPred

1.0

GERP RS

5.3

Varity_R

0.87

gMVP

0.88

Mutation Taster

=17/83

disease causing

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over