NM_006002.5:c.183+1631G>A

Variant names:

• chr13-75562512-G-A
• rs9543976
• NM_006002.5:c.183+1631G>A

Variant summary

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

The NM_006002.5(UCHL3):​c.183+1631G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 151,858 control chromosomes in the GnomAD database, including 42,345 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 0.72 (42345 hom., cov: 31)
• Consequence: UCHL3 NM_006002.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460
• Publications: 18 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UCHL3	NM_006002.5	c.183+1631G>A		intron_variant	Intron 3 of 8	ENST00000377595.8	NP_005993.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UCHL3	ENST00000377595.8	c.183+1631G>A		intron_variant	Intron 3 of 8	1	NM_006002.5	ENSP00000366819.3
UCHL3	ENST00000471792.6	n.329+1631G>A		intron_variant	Intron 3 of 6	3
ENSG00000261553	ENST00000563635.5	n.231+1631G>A		intron_variant	Intron 3 of 14	5

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109306 AN: 151740 Hom.: 42359 Cov.: 31

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.800

Gnomad FIN AF: 0.901

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.868

Gnomad OTH AF: 0.734

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

GnomAD4 genome AF: 0.720 AC: 109329 AN: 151858 Hom.: 42345 Cov.: 31 AF XY: 0.722 AC XY: 53534 AN XY: 74196

African (AFR) AF: 0.428 AC: 17730 AN: 41384

American (AMR) AF: 0.663 AC: 10131 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.831 AC: 2882 AN: 3468

East Asian (EAS) AF: 0.712 AC: 3673 AN: 5162

South Asian (SAS) AF: 0.799 AC: 3847 AN: 4812

European-Finnish (FIN) AF: 0.901 AC: 9522 AN: 10574

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.868 AC: 58918 AN: 67872

Other (OTH) AF: 0.732 AC: 1546 AN: 2112

Alfa AF: 0.819 Hom.: 195242

Bravo AF: 0.689

Asia WGS AF: 0.697 AC: 2405 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.14
DANN	Benign	0.45
PhyloP100		-0.046
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: rs9543976; hg19: chr13-76136648;