17-7565912-C-T

Variant names:

• chr17-7565912-C-T
• rs11078697
• NM_015670.6:c.1263+148C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.470

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

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	c.1263+148C>T		intron_variant	Intron 6 of 10	ENST00000321337.12	NP_056485.2
SENP3-EIF4A1	NR_037926.1	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	c.1263+148C>T		intron_variant	Intron 6 of 10	1	NM_015670.6	ENSP00000314029.8
SENP3-EIF4A1	ENST00000614237.1	n.1053+148C>T		intron_variant	Intron 5 of 20	2		ENSP00000483614.1

Frequencies

GnomAD3 genomes AF: 0.0289 AC: 4391 AN: 152066 Hom.: 238 Cov.: 32

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.: 6 AF XY: 0.0353 AC XY: 9403 AN XY: 266410

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.: 32 AF XY: 0.0329 AC XY: 2451 AN XY: 74396

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

Other links and lift over

dbSNP: rs11078697; hg19: chr17-7469229;