chr12-48047965-G-A

Position:

• chr12-48047965-G-A

Variant summary

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

The NM_001267594.2(SENP1):​c.1691+36C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0887 in 1,376,252 control chromosomes in the GnomAD database, including 6,273 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 0.094 (767 hom., cov: 32)
  • Exomes 𝑓: 0.088 (5506 hom.)
• Consequence: SENP1 NM_001267594.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100

Genes affected

SENP1 (HGNC:17927): (SUMO specific peptidase 1) This gene encodes a cysteine protease that specifically targets members of the small ubiquitin-like modifier (SUMO) protein family. This protease regulates SUMO pathways by deconjugating sumoylated proteins. This protease also functions to process the precursor SUMO proteins into their mature form. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SENP1	NM_001267594.2	c.1691+36C>T		intron_variant		ENST00000549518.6	NP_001254523.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SENP1	ENST00000549518.6	c.1691+36C>T		intron_variant		1	NM_001267594.2	ENSP00000447328	P4
SENP1	ENST00000448372.6	c.1691+36C>T		intron_variant		1		ENSP00000394791	P4
SENP1	ENST00000552189.5	c.*1429+36C>T		intron_variant, NMD_transcript_variant		1		ENSP00000447593
SENP1	ENST00000549595.5	c.1691+36C>T		intron_variant		5		ENSP00000450076	A1

Frequencies

GnomAD3 genomes AF: 0.0934 AC: 14190 AN: 151960 Hom.: 762 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0528

Gnomad ASJ AF: 0.0482

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0164

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0979

Gnomad OTH AF: 0.0757

GnomAD3 exomes AF: 0.0720 AC: 17483 AN: 242868 Hom.: 843 AF XY: 0.0703 AC XY: 9244 AN XY: 131584

Gnomad AFR exome AF: 0.120

Gnomad AMR exome AF: 0.0335

Gnomad ASJ exome AF: 0.0504

Gnomad EAS exome AF: 0.000395

Gnomad SAS exome AF: 0.0204

Gnomad FIN exome AF: 0.110

Gnomad NFE exome AF: 0.0965

Gnomad OTH exome AF: 0.0702

GnomAD4 exome AF: 0.0881 AC: 107883 AN: 1224174 Hom.: 5506 Cov.: 17 AF XY: 0.0855 AC XY: 53035 AN XY: 620556

Gnomad4 AFR exome AF: 0.119

Gnomad4 AMR exome AF: 0.0350

Gnomad4 ASJ exome AF: 0.0522

Gnomad4 EAS exome AF: 0.000545

Gnomad4 SAS exome AF: 0.0208

Gnomad4 FIN exome AF: 0.112

Gnomad4 NFE exome AF: 0.0997

Gnomad4 OTH exome AF: 0.0810

GnomAD4 genome AF: 0.0935 AC: 14220 AN: 152078 Hom.: 767 Cov.: 32 AF XY: 0.0918 AC XY: 6828 AN XY: 74360

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.0528

Gnomad4 ASJ AF: 0.0482

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0166

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.0979

Gnomad4 OTH AF: 0.0750

Alfa AF: 0.0898 Hom.: 526

Bravo AF: 0.0892

Asia WGS AF: 0.0240 AC: 83 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.16
DANN	Benign	0.48

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: rs12297820; hg19: chr12-48441748;