rs1597838496

Variant names:

• chr17-7563762-C-T
• rs1597838496
• NM_015670.6:c.686C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-7563762-C-T
• chr17-7563762-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015670.6(SENP3):​c.686C>T​(p.Thr229Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,459,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SENP3 NM_015670.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.50
• Publications: 0 publications found

Genes affected

SENP3 (HGNC:17862): (SUMO specific peptidase 3) The reversible posttranslational modification of proteins by the addition of small ubiquitin-like SUMO proteins (see SUMO1; MIM 601912) is required for numerous biologic processes. SUMO-specific proteases, such as SENP3, are responsible for the initial processing of SUMO precursors to generate a C-terminal diglycine motif required for the conjugation reaction. They also have isopeptidase activity for the removal of SUMO from high molecular mass SUMO conjugates (Di Bacco et al., 2006 [PubMed 16738315]).[supplied by OMIM, Jun 2009]

SENP3-EIF4A1 (HGNC:49182): (SENP3-EIF4A1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring SUMO1/sentrin/SMT3 specific peptidase 3 (SENP3) and eukaryotic translation initiation factor 4A1 (EIF4A1) genes on chromosome 17. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Mar 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13414696).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015670.6. 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
	SENP3	NM_015670.6	MANE Select	c.686C>T	p.Thr229Ile	missense	Exon 2 of 11	NP_056485.2
	SENP3-EIF4A1	NR_037926.1		n.969C>T		non_coding_transcript_exon	Exon 2 of 22

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SENP3	ENST00000321337.12	TSL:1 MANE Select	c.686C>T	p.Thr229Ile	missense	Exon 2 of 11	ENSP00000314029.8	Q9H4L4
	SENP3-EIF4A1	ENST00000614237.1	TSL:2	n.476C>T		non_coding_transcript_exon	Exon 1 of 21	ENSP00000483614.1	A0A087X0R7
	SENP3	ENST00000937871.1		c.686C>T	p.Thr229Ile	missense	Exon 1 of 10	ENSP00000607930.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1459870 Hom.: 0 Cov.: 46 AF XY: 0.00000275 AC XY: 2 AN XY: 726234

African (AFR) AF: 0.0000299 AC: 1 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.00 AC: 0 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5608

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111560

Other (OTH) AF: 0.00 AC: 0 AN: 60290

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.18
Eigen_PC	Benign	0.044
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.5
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.17
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.073	T
Polyphen		0.011	B
Vest4		0.27
MutPred		0.15		Loss of phosphorylation at T229 (P = 0.0073)
MVP		0.45
MPC		0.28
ClinPred		0.59	D
GERP RS		4.4
Varity_R		0.15
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1597838496; hg19: chr17-7467079; COSMIC: COSV53436952; COSMIC: COSV53436952;