3-185609340-A-G

Variant names:

• chr3-185609340-A-G
• rs79193891
• NM_021627.3:c.712A>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_021627.3(SENP2):​c.712A>G​(p.Asn238Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000516 in 1,609,774 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0027 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00029 (1 hom.)
• Consequence: SENP2 NM_021627.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.670
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0039334595).
• BP6: Variant 3-185609340-A-G is Benign according to our data. Variant chr3-185609340-A-G is described in ClinVar as Benign. ClinVar VariationId is 709755.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 412 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021627.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SENP2	NM_021627.3	MANE Select	c.712A>G	p.Asn238Asp	missense	Exon 7 of 17	NP_067640.2	Q9HC62-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SENP2	ENST00000296257.10	TSL:1 MANE Select	c.712A>G	p.Asn238Asp	missense	Exon 7 of 17	ENSP00000296257.5	Q9HC62-1
	SENP2	ENST00000953470.1		c.712A>G	p.Asn238Asp	missense	Exon 7 of 17	ENSP00000623529.1
	SENP2	ENST00000953471.1		c.712A>G	p.Asn238Asp	missense	Exon 7 of 17	ENSP00000623530.1

Frequencies

GnomAD3 genomes AF: 0.00265 AC: 404 AN: 152226 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00921

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

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: 0.0000294

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000642 AC: 161 AN: 250804 AF XY: 0.000465

Gnomad AFR exome AF: 0.00825

Gnomad AMR exome AF: 0.000553

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000287 AC: 419 AN: 1457430 Hom.: 1 Cov.: 28 AF XY: 0.000267 AC XY: 194 AN XY: 725286

African (AFR) AF: 0.00878 AC: 293 AN: 33362

American (AMR) AF: 0.000560 AC: 25 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26094

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39634

South Asian (SAS) AF: 0.0000349 AC: 3 AN: 86034

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5748

European-Non Finnish (NFE) AF: 0.0000550 AC: 61 AN: 1108262

Other (OTH) AF: 0.000581 AC: 35 AN: 60266

GnomAD4 genome AF: 0.00270 AC: 412 AN: 152344 Hom.: 1 Cov.: 32 AF XY: 0.00277 AC XY: 206 AN XY: 74502

African (AFR) AF: 0.00938 AC: 390 AN: 41582

American (AMR) AF: 0.00111 AC: 17 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68034

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00100 Hom.: 3

Bravo AF: 0.00280

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00726 AC: 32

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000749 AC: 91

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.35
DANN	Benign	0.43
DEOGEN2	Benign	0.022	T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.14	N
PhyloP100		-0.67
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.23	N
REVEL	Benign	0.023
Sift	Benign	1.0	T
Sift4G	Benign	0.82	T
Polyphen		0.0040	B
Vest4		0.11
MVP		0.39
MPC		0.48
ClinPred		0.0080	T
GERP RS		-11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.024
gMVP		0.065
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs79193891; hg19: chr3-185327128; COSMIC: COSV99957681; COSMIC: COSV99957681;