rs989144

Variant names:

• chr12-48090190-T-C
• rs989144
• NM_001267594.2:c.221-1230A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001267594.2(SENP1):​c.221-1230A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,248 control chromosomes in the GnomAD database, including 2,442 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 0.17 (2442 hom., cov: 32)
• Consequence: SENP1 NM_001267594.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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 = 0.265 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001267594.2. 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
	SENP1	NM_001267594.2	MANE Select	c.221-1230A>G		intron	N/A	NP_001254523.1	Q9P0U3-1
	SENP1	NM_001267595.2		c.221-1230A>G		intron	N/A	NP_001254524.1	Q9P0U3-1
	SENP1	NR_051991.1		n.856-897A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SENP1	ENST00000549518.6	TSL:1 MANE Select	c.221-1230A>G		intron	N/A	ENSP00000447328.1	Q9P0U3-1
	SENP1	ENST00000448372.6	TSL:1	c.221-1230A>G		intron	N/A	ENSP00000394791.2	Q9P0U3-1
	SENP1	ENST00000552189.5	TSL:1	n.221-897A>G		intron	N/A	ENSP00000447593.1	F8W0I8

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25346 AN: 152130 Hom.: 2441 Cov.: 32

Gnomad AFR AF: 0.0747

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.204

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.166 AC: 25346 AN: 152248 Hom.: 2442 Cov.: 32 AF XY: 0.164 AC XY: 12186 AN XY: 74442

African (AFR) AF: 0.0747 AC: 3104 AN: 41540

American (AMR) AF: 0.180 AC: 2746 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 943 AN: 3466

East Asian (EAS) AF: 0.277 AC: 1433 AN: 5174

South Asian (SAS) AF: 0.149 AC: 720 AN: 4830

European-Finnish (FIN) AF: 0.128 AC: 1361 AN: 10610

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14459 AN: 68016

Other (OTH) AF: 0.203 AC: 427 AN: 2108

Alfa AF: 0.195 Hom.: 6246

Bravo AF: 0.166

Asia WGS AF: 0.173 AC: 600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.092
DANN	Benign	0.67
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs989144; hg19: chr12-48483973;