Genetic Variant NM_015670.6:c.1263+148C>T (chr17-7565912-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015670.6(SENP3):c.1263+148C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0348 in 666,388 control chromosomes in the GnomAD database, including 1,773 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.029 ( 239 hom., cov: 32)

Exomes 𝑓: 0.037 ( 1534 hom. )

Consequence

SENP3
NM_015670.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.470

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SENP3	NM_015670.6 link	c.1263+148C>T		intron_variant	Intron 6 of 10	ENST00000321337.12	NP_056485.2	Q9H4L4
SENP3-EIF4A1	NR_037926.1 link	n.1546+148C>T		intron_variant	Intron 6 of 21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SENP3	ENST00000321337.12 link	c.1263+148C>T		intron_variant	Intron 6 of 10	1	NM_015670.6	ENSP00000314029.8		Q9H4L4
SENP3-EIF4A1	ENST00000614237.1 link	n.1053+148C>T		intron_variant	Intron 5 of 20	2		ENSP00000483614.1		A0A087X0R7

Frequencies

GnomAD3 genomes

AF:

0.0289

AC:

4391

AN:

152066

Hom.:

238

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00466

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.0875

Gnomad ASJ

AF:

0.0256

Gnomad EAS

AF:

0.228

Gnomad SAS

AF:

0.0255

Gnomad FIN

AF:

0.0332

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0151

Gnomad OTH

AF:

0.0288

GnomAD4 exome

AF:

0.0365

AC:

18788

AN:

514204

Hom.:

1534

Cov.:

AF XY:

0.0353

AC XY:

9403

AN XY:

266410

show subpopulations

Gnomad4 AFR exome

AF:

0.00363

Gnomad4 AMR exome

AF:

0.104

Gnomad4 ASJ exome

AF:

0.0205

Gnomad4 EAS exome

AF:

0.283

Gnomad4 SAS exome

AF:

0.0228

Gnomad4 FIN exome

AF:

0.0326

Gnomad4 NFE exome

AF:

0.0140

Gnomad4 OTH exome

AF:

0.0271

GnomAD4 genome

AF:

0.0289

AC:

4405

AN:

152184

Hom.:

239

Cov.:

AF XY:

0.0329

AC XY:

2451

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.00465

Gnomad4 AMR

AF:

0.0880

Gnomad4 ASJ

AF:

0.0256

Gnomad4 EAS

AF:

0.229

Gnomad4 SAS

AF:

0.0261

Gnomad4 FIN

AF:

0.0332

Gnomad4 NFE

AF:

0.0151

Gnomad4 OTH

AF:

0.0289

Alfa

AF:

0.0213

Hom.:

110

Bravo

AF:

0.0354

Asia WGS

AF:

0.0970

AC:

339

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

7.9

DANN

Benign

0.80

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over