chr3-196885683-A-T

Variant names:

• chr3-196885683-A-T
• rs1412617876
• NM_152699.5:c.502A>T

Variant summary

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

The NM_152699.5(SENP5):​c.502A>T​(p.Met168Leu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SENP5 NM_152699.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.50
• Publications: 0 publications found

Genes affected

SENP5 (HGNC:28407): (SUMO specific peptidase 5) The reversible posttranslational modification of proteins by the addition of small ubiquitin-like SUMO proteins (see SUMO1; MIM 601912) is required for numerous biologic processes. SUMO-specific proteases, such as SENP5, are responsible for the initial processing of SUMO precursors to generate a C-terminal diglycine motif required for the conjugation reaction. They also have isopeptidase activity for the removal of SUMO from high molecular mass SUMO conjugates (Di Bacco et al., 2006 [PubMed 16738315]).[supplied by OMIM, Jun 2009]

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=0.14066392).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152699.5. 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
	SENP5	NM_152699.5	MANE Select	c.502A>T	p.Met168Leu	missense	Exon 2 of 10	NP_689912.2	Q96HI0-1
	SENP5	NM_001308045.2		c.502A>T	p.Met168Leu	missense	Exon 2 of 9	NP_001294974.1	Q96HI0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SENP5	ENST00000323460.10	TSL:1 MANE Select	c.502A>T	p.Met168Leu	missense	Exon 2 of 10	ENSP00000327197.5	Q96HI0-1
	SENP5	ENST00000875329.1		c.502A>T	p.Met168Leu	missense	Exon 3 of 11	ENSP00000545388.1
	SENP5	ENST00000946893.1		c.502A>T	p.Met168Leu	missense	Exon 3 of 11	ENSP00000616952.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251006 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Benign	0.94
DEOGEN2	Benign	0.0054	T
Eigen	Benign	-0.15
Eigen_PC	Benign	0.031
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		3.5
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.12
Sift	Uncertain	0.018	D
Sift4G	Benign	0.40	T
Polyphen		0.085	B
Vest4		0.37
MutPred		0.21		Gain of catalytic residue at M168 (P = 0.0281)
MVP		0.37
MPC		0.49
ClinPred		0.45	T
GERP RS		4.0
Varity_R		0.35
gMVP		0.21
Mutation Taster		=95/5	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: rs1412617876; hg19: chr3-196612554;