13-75597195-A-G

Variant names:

• chr13-75597195-A-G
• rs4885322
• NM_006002.5:c.550+2205A>G

Variant summary

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

The NM_006002.5(UCHL3):​c.550+2205A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 151,966 control chromosomes in the GnomAD database, including 45,957 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 0.77 (45957 hom., cov: 29)
• Consequence: UCHL3 NM_006002.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.769
• Publications: 4 publications found

Genes affected

UCHL3 (HGNC:12515): (ubiquitin C-terminal hydrolase L3) The protein encoded by this gene is a member of the deubiquitinating enzyme family. Members of this family are proteases that catalyze the removal of ubiquitin from polypeptides and are divided into five classes, depending on the mechanism of catalysis. This protein may hydrolyze the ubiquitinyl-N-epsilon amide bond of ubiquitinated proteins to regenerate ubiquitin for another catalytic cycle. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Aug 2012]

ENSG00000261553 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006002.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UCHL3	NM_006002.5	MANE Select	c.550+2205A>G		intron	N/A	NP_005993.1
	UCHL3	NM_001270952.2		c.442+2205A>G		intron	N/A	NP_001257881.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UCHL3	ENST00000377595.8	TSL:1 MANE Select	c.550+2205A>G		intron	N/A	ENSP00000366819.3
	UCHL3	ENST00000419068.1	TSL:5	c.544+2205A>G		intron	N/A	ENSP00000398189.1
	ENSG00000261553	ENST00000563635.5	TSL:5	n.598+2205A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.771 AC: 117147 AN: 151848 Hom.: 45954 Cov.: 29

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.875

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.878

Gnomad MID AF: 0.885

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.781

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

GnomAD4 genome AF: 0.771 AC: 117195 AN: 151966 Hom.: 45957 Cov.: 29 AF XY: 0.772 AC XY: 57347 AN XY: 74276

African (AFR) AF: 0.650 AC: 26885 AN: 41382

American (AMR) AF: 0.678 AC: 10355 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.826 AC: 2865 AN: 3470

East Asian (EAS) AF: 0.710 AC: 3666 AN: 5160

South Asian (SAS) AF: 0.789 AC: 3794 AN: 4808

European-Finnish (FIN) AF: 0.878 AC: 9292 AN: 10582

Middle Eastern (MID) AF: 0.884 AC: 258 AN: 292

European-Non Finnish (NFE) AF: 0.848 AC: 57638 AN: 67984

Other (OTH) AF: 0.778 AC: 1644 AN: 2112

Alfa AF: 0.824 Hom.: 26441

Bravo AF: 0.750

Asia WGS AF: 0.708 AC: 2460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.2
DANN	Benign	0.43
PhyloP100		0.77
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: rs4885322; hg19: chr13-76171331;