chr12-48065129-T-G

Variant names:

• chr12-48065129-T-G
• rs182987633
• NM_001267594.2:c.1211A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001267594.2(SENP1):​c.1211A>C​(p.Gln404Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q404R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SENP1 NM_001267594.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.710
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12541565).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SENP1	NM_001267594.2	c.1211A>C	p.Gln404Pro	missense_variant	Exon 12 of 18	ENST00000549518.6	NP_001254523.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SENP1	ENST00000549518.6	c.1211A>C	p.Gln404Pro	missense_variant	Exon 12 of 18	1	NM_001267594.2	ENSP00000447328.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.055	T;.;T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.66	.;T;T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.39	N;N;N
PhyloP100		0.71
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.45	N;N;N
REVEL	Benign	0.037
Sift	Benign	0.51	T;T;T
Sift4G	Benign	0.43	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.23
MutPred		0.34		Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);
MVP		0.40
ClinPred		0.062	T
GERP RS		1.4
Varity_R		0.093
gMVP		0.31
Mutation Taster		=80/20	polymorphism

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: rs182987633; hg19: chr12-48458912;