3-185613377-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_021627.3(SENP2):c.902C>T(p.Thr301Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000378 in 1,586,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T301K) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: SENP2 NM_021627.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38

Genes affected

SENP2 (HGNC:23116): (SUMO specific peptidase 2) SUMO1 (UBL1; MIM 601912) is a small ubiquitin-like protein that can be covalently conjugated to other proteins. SENP2 is one of a group of enzymes that process newly synthesized SUMO1 into the conjugatable form and catalyze the deconjugation of SUMO1-containing species.[supplied by OMIM, Apr 2004]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.054368258).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SENP2	NM_021627.3	c.902C>T	p.Thr301Met	missense_variant	10/17	ENST00000296257.10
SENP2	XM_005247690.4	c.902C>T	p.Thr301Met	missense_variant	10/16
SENP2	XM_005247691.4	c.557C>T	p.Thr186Met	missense_variant	8/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SENP2	ENST00000296257.10	c.902C>T	p.Thr301Met	missense_variant	10/17	1	NM_021627.3	P1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151874 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000121 AC: 3 AN: 248050 Hom.: 0 AF XY: 0.0000149 AC XY: 2 AN XY: 134010

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000165

Gnomad SAS 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: 0.00000349 AC: 5 AN: 1434300 Hom.: 0 Cov.: 27 AF XY: 0.00000280 AC XY: 2 AN XY: 714786

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000275

Gnomad4 OTH exome AF: 0.0000168

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151874 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74170

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000549

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.54
Cadd	Benign	16
Dann	Benign	0.97
DEOGEN2	Benign	0.026	T;T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.60	T;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.054	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.31	N;N
REVEL	Benign	0.037
Sift	Uncertain	0.012	D;D
Sift4G	Benign	0.11	T;T
Polyphen		0.040	B;.
Vest4		0.065
MVP		0.10
MPC		0.43
ClinPred		0.083	T
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.019
gMVP		0.47

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

LitVar

Other links and lift over

dbSNP: rs6762208; hg19: chr3-185331165; COSMIC: COSV99958461; COSMIC: COSV99958461;