3-101326018-T-C

Variant names:

• chr3-101326018-T-C
• NM_020654.5:c.3078A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020654.5(SENP7):​c.3078A>G​(p.Ile1026Met) 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. 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: 0.461

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16230196).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SENP7	NM_020654.5	c.3078A>G	p.Ile1026Met	missense_variant	Exon 24 of 24	ENST00000394095.7	NP_065705.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SENP7	ENST00000394095.7	c.3078A>G	p.Ile1026Met	missense_variant	Exon 24 of 24	1	NM_020654.5	ENSP00000377655.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 12, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3078A>G (p.I1026M) alteration is located in exon 24 (coding exon 24) of the SENP7 gene. This alteration results from a A to G substitution at nucleotide position 3078, causing the isoleucine (I) at amino acid position 1026 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0050	T;.;T;.;.;.
Eigen	Benign	0.092
Eigen_PC	Benign	0.088
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.80	T;T;T;T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.16	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;.;.;.;.;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.7	N;N;N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.068	T;T;T;T;T;T
Sift4G	Benign	0.62	T;T;T;T;T;T
Polyphen		1.0	D;D;.;D;B;D
Vest4		0.15
MutPred		0.48		Loss of methylation at K1027 (P = 0.0182);.;.;.;.;.;
MVP		0.27
MPC		2.0
ClinPred		0.82	D
GERP RS		1.2
Varity_R		0.34
gMVP		0.58

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-101044862;