chr3-101328672-C-T

Variant names:

• chr3-101328672-C-T
• rs2058968104
• NM_020654.5:c.2769G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020654.5(SENP7):​c.2769G>A​(p.Met923Ile) 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. 15/21 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: -0.295

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.026830286).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SENP7	NM_020654.5	c.2769G>A	p.Met923Ile	missense_variant	Exon 21 of 24	ENST00000394095.7	NP_065705.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SENP7	ENST00000394095.7	c.2769G>A	p.Met923Ile	missense_variant	Exon 21 of 24	1	NM_020654.5	ENSP00000377655.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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 24, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2769G>A (p.M923I) alteration is located in exon 21 (coding exon 21) of the SENP7 gene. This alteration results from a G to A substitution at nucleotide position 2769, causing the methionine (M) at amino acid position 923 to be replaced by an isoleucine (I). 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	Benign	0.11
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.4
DANN	Benign	0.89
DEOGEN2	Benign	0.00018	T;.;T;.;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0057	N
LIST_S2	Benign	0.71	T;T;T;T;T;T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.027	T;T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.2	N;.;.;.;.;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.070	N;N;N;N;N;N
REVEL	Benign	0.014
Sift	Benign	0.51	T;T;T;T;T;T
Sift4G	Benign	0.40	T;T;T;T;T;T
Polyphen		0.0	B;B;.;B;B;B
Vest4		0.090
MutPred		0.32		Loss of catalytic residue at M923 (P = 0.0122);.;.;.;.;.;
MVP		0.16
MPC		0.94
ClinPred		0.047	T
GERP RS		-1.6
Varity_R		0.029
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2058968104; hg19: chr3-101047516;