12-48081070-A-G

Variant names:

• chr12-48081070-A-G
• rs10492081
• NM_001267594.2:c.552+2521T>C

Variant summary

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

The NM_001267594.2(SENP1):​c.552+2521T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 151,882 control chromosomes in the GnomAD database, including 4,777 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 0.24 (4777 hom., cov: 31)
• Consequence: SENP1 NM_001267594.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0950

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]

RNU6-1203P (HGNC:48166): (RNA, U6 small nuclear 1203, pseudogene)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SENP1	NM_001267594.2	c.552+2521T>C		intron_variant	Intron 6 of 17	ENST00000549518.6	NP_001254523.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SENP1	ENST00000549518.6	c.552+2521T>C		intron_variant	Intron 6 of 17	1	NM_001267594.2	ENSP00000447328.1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35694 AN: 151764 Hom.: 4777 Cov.: 31

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.235 AC: 35710 AN: 151882 Hom.: 4777 Cov.: 31 AF XY: 0.234 AC XY: 17369 AN XY: 74236

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.258

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.207

Alfa AF: 0.189 Hom.: 3828

Bravo AF: 0.246

Asia WGS AF: 0.237 AC: 825 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	9.2
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs10492081; hg19: chr12-48474853;