Genetic Variant NM_015670.6:c.79C>T (chr17-7563155-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015670.6(SENP3):c.79C>T(p.Pro27Ser) 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. 13/21 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. P27A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

SENP3
NM_015670.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.38

Publications

1 publications found

Variant links:

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 links:

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]

SENP3-EIF4A1 links:

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ACMG classification

Classification was made for transcript

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=0.24171579).

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.79C>T	p.Pro27Ser	missense	Exon 2 of 11	NP_056485.2
	SENP3-EIF4A1	NR_037926.1		n.362C>T		non_coding_transcript_exon	Exon 2 of 22

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SENP3	ENST00000321337.12	TSL:1 MANE Select	c.79C>T	p.Pro27Ser	missense	Exon 2 of 11	ENSP00000314029.8	Q9H4L4
SENP3	ENST00000937871.1		c.79C>T	p.Pro27Ser	missense	Exon 1 of 10	ENSP00000607930.1
SENP3	ENST00000937872.1		c.79C>T	p.Pro27Ser	missense	Exon 2 of 10	ENSP00000607931.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

195576

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

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

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000830

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.071

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.82

M_CAP

Benign

0.014

MetaRNN

Benign

0.24

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

3.4

PrimateAI

Uncertain

0.65

PROVEAN

Benign

0.39

REVEL

Benign

0.13

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.98

Vest4

0.39

MutPred

0.15

Gain of phosphorylation at P27 (P = 0.005)

MVP

0.34

MPC

0.27

ClinPred

0.59

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.17

gMVP

0.55

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over