chr3-196885537-T-A

Variant names:

• chr3-196885537-T-A
• rs150432878
• NM_152699.5:c.356T>A

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.356T>A​(p.Leu119Gln) 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. 15/22 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. L119P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SENP5 NM_152699.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• 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=0.13788179).

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.356T>A	p.Leu119Gln	missense	Exon 2 of 10	NP_689912.2	Q96HI0-1
	SENP5	NM_001308045.2		c.356T>A	p.Leu119Gln	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.356T>A	p.Leu119Gln	missense	Exon 2 of 10	ENSP00000327197.5	Q96HI0-1
	SENP5	ENST00000875329.1		c.356T>A	p.Leu119Gln	missense	Exon 3 of 11	ENSP00000545388.1
	SENP5	ENST00000946893.1		c.356T>A	p.Leu119Gln	missense	Exon 3 of 11	ENSP00000616952.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
PhyloP100		1.3
Varity_R		0.38
gMVP		0.19
Mutation Taster		=88/12	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs150432878; hg19: chr3-196612408;