12-48073938-A-G

Variant names:

• chr12-48073938-A-G
• rs1978161
• NM_001267594.2:c.940+386T>C

Variant summary

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

The NM_001267594.2(SENP1):​c.940+386T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 152,046 control chromosomes in the GnomAD database, including 12,937 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 0.40 (12937 hom., cov: 32)
• Consequence: SENP1 NM_001267594.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179
• Publications: 4 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SENP1	NM_001267594.2	c.940+386T>C		intron_variant	Intron 8 of 17	ENST00000549518.6	NP_001254523.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SENP1	ENST00000549518.6	c.940+386T>C		intron_variant	Intron 8 of 17	1	NM_001267594.2	ENSP00000447328.1
SENP1	ENST00000448372.6	c.940+386T>C		intron_variant	Intron 8 of 17	1		ENSP00000394791.2
SENP1	ENST00000552189.5	n.*678+386T>C		intron_variant	Intron 9 of 18	1		ENSP00000447593.1
SENP1	ENST00000549595.5	c.940+386T>C		intron_variant	Intron 7 of 16	5		ENSP00000450076.1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60550 AN: 151928 Hom.: 12922 Cov.: 32

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.431

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

GnomAD4 genome AF: 0.399 AC: 60605 AN: 152046 Hom.: 12937 Cov.: 32 AF XY: 0.405 AC XY: 30118 AN XY: 74314

African (AFR) AF: 0.316 AC: 13117 AN: 41478

American (AMR) AF: 0.547 AC: 8357 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1643 AN: 3468

East Asian (EAS) AF: 0.830 AC: 4297 AN: 5180

South Asian (SAS) AF: 0.501 AC: 2416 AN: 4824

European-Finnish (FIN) AF: 0.363 AC: 3831 AN: 10562

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.377 AC: 25606 AN: 67940

Other (OTH) AF: 0.435 AC: 920 AN: 2116

Alfa AF: 0.379 Hom.: 1833

Bravo AF: 0.410

Asia WGS AF: 0.614 AC: 2127 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.4
DANN	Benign	0.70
PhyloP100		0.18
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: rs1978161; hg19: chr12-48467721;