3-101332000-C-T

Variant names:

• chr3-101332000-C-T
• rs757905357
• NM_020654.5:c.2683G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_020654.5(SENP7):​c.2683G>A​(p.Asp895Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,613,296 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: SENP7 NM_020654.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.295
• 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08498058).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SENP7	NM_020654.5	c.2683G>A	p.Asp895Asn	missense_variant	Exon 19 of 24	ENST00000394095.7	NP_065705.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SENP7	ENST00000394095.7	c.2683G>A	p.Asp895Asn	missense_variant	Exon 19 of 24	1	NM_020654.5	ENSP00000377655.2

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152026 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251062 AF XY: 0.00000737

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000890 AC: 13 AN: 1461152 Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4 AN XY: 726878

African (AFR) AF: 0.000269 AC: 9 AN: 33448

American (AMR) AF: 0.0000224 AC: 1 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39604

South Asian (SAS) AF: 0.00 AC: 0 AN: 86216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111576

Other (OTH) AF: 0.0000497 AC: 3 AN: 60350

GnomAD4 genome AF: 0.0000789 AC: 12 AN: 152144 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74380

African (AFR) AF: 0.000265 AC: 11 AN: 41506

American (AMR) AF: 0.0000655 AC: 1 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000153 Hom.: 0

Bravo AF: 0.000125

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2683G>A (p.D895N) alteration is located in exon 19 (coding exon 19) of the SENP7 gene. This alteration results from a G to A substitution at nucleotide position 2683, causing the aspartic acid (D) at amino acid position 895 to be replaced by an asparagine (N). 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	0.069
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0044	T;.;T;.;.;.
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.84	T;T;T;T;T;T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.085	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;.;.;.;.;.
PhyloP100		0.29
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.4	N;N;N;N;N;N
REVEL	Benign	0.063
Sift	Benign	0.071	T;T;D;T;T;T
Sift4G	Uncertain	0.043	D;T;T;T;T;T
Polyphen		0.0040	B;B;.;B;B;B
Vest4		0.081
MVP		0.26
MPC		0.86
ClinPred		0.093	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.082
gMVP		0.47
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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

dbSNP: rs757905357; hg19: chr3-101050844; COSMIC: COSV107387908;