chr13-75597195-A-G

Position:

• chr13-75597195-A-G

Variant summary

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

The ENST00000377595.8(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 ENST00000377595.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.769

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UCHL3	NM_006002.5	c.550+2205A>G		intron_variant		ENST00000377595.8	NP_005993.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UCHL3	ENST00000377595.8	c.550+2205A>G		intron_variant		1	NM_006002.5	ENSP00000366819	P1
UCHL3	ENST00000419068.1	c.544+2205A>G		intron_variant		5		ENSP00000398189
UCHL3	ENST00000606347.1	n.461+2205A>G		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.650

Gnomad4 AMR AF: 0.678

Gnomad4 ASJ AF: 0.826

Gnomad4 EAS AF: 0.710

Gnomad4 SAS AF: 0.789

Gnomad4 FIN AF: 0.878

Gnomad4 NFE AF: 0.848

Gnomad4 OTH AF: 0.778

Alfa AF: 0.824 Hom.: 23524

Bravo AF: 0.750

Asia WGS AF: 0.708 AC: 2460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.2
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs4885322; hg19: chr13-76171331;