rs7324560

Variant names:

• chr13-75588744-A-G
• rs7324560
• NM_006002.5:c.475-6171A>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.475-6171A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,190 control chromosomes in the GnomAD database, including 1,178 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 0.11 (1178 hom., cov: 32)
• Consequence: UCHL3 NM_006002.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180
• Publications: 3 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UCHL3	NM_006002.5	c.475-6171A>G		intron_variant	Intron 6 of 8	ENST00000377595.8	NP_005993.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UCHL3	ENST00000377595.8	c.475-6171A>G		intron_variant	Intron 6 of 8	1	NM_006002.5	ENSP00000366819.3

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16811 AN: 152070 Hom.: 1178 Cov.: 32

Gnomad AFR AF: 0.0452

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.0920

Gnomad ASJ AF: 0.0891

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0723

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.111 AC: 16831 AN: 152190 Hom.: 1178 Cov.: 32 AF XY: 0.110 AC XY: 8173 AN XY: 74416

African (AFR) AF: 0.0455 AC: 1889 AN: 41548

American (AMR) AF: 0.0917 AC: 1403 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0891 AC: 309 AN: 3468

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5182

South Asian (SAS) AF: 0.0724 AC: 349 AN: 4820

European-Finnish (FIN) AF: 0.163 AC: 1727 AN: 10586

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10845 AN: 67972

Other (OTH) AF: 0.106 AC: 224 AN: 2112

Alfa AF: 0.134 Hom.: 204

Bravo AF: 0.102

Asia WGS AF: 0.0420 AC: 145 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.5
DANN	Benign	0.75
PhyloP100		-0.018
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: rs7324560; hg19: chr13-76162880;