rs10517002

Variant names:

• chr4-41262532-C-A
• rs10517002
• NM_004181.5:c.459+609C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-41262532-C-A
• chr4-41262532-C-G
• chr4-41262532-C-T

Variant summary

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

The NM_004181.5(UCHL1):​c.459+609C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 151,786 control chromosomes in the GnomAD database, including 26,708 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 0.59 (26708 hom., cov: 31)
• Consequence: UCHL1 NM_004181.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104
• Publications: 5 publications found

Genes affected

UCHL1 (HGNC:12513): (ubiquitin C-terminal hydrolase L1) The protein encoded by this gene belongs to the peptidase C12 family. This enzyme is a thiol protease that hydrolyzes a peptide bond at the C-terminal glycine of ubiquitin. This gene is specifically expressed in the neurons and in cells of the diffuse neuroendocrine system. Mutations in this gene may be associated with Parkinson disease.[provided by RefSeq, Sep 2009]

UCHL1 Gene-Disease associations (from GenCC):

• spastic paraplegia 79A, autosomal dominant, with ataxia

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• Parkinson disease 5, autosomal dominant, susceptibility to

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

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 (EAS) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UCHL1	NM_004181.5	c.459+609C>A		intron_variant	Intron 6 of 8	ENST00000284440.9	NP_004172.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UCHL1	ENST00000284440.9	c.459+609C>A		intron_variant	Intron 6 of 8	1	NM_004181.5	ENSP00000284440.4

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89637 AN: 151668 Hom.: 26665 Cov.: 31

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.790

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.603

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

GnomAD4 genome AF: 0.591 AC: 89724 AN: 151786 Hom.: 26708 Cov.: 31 AF XY: 0.590 AC XY: 43778 AN XY: 74140

African (AFR) AF: 0.550 AC: 22735 AN: 41346

American (AMR) AF: 0.626 AC: 9552 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 2094 AN: 3470

East Asian (EAS) AF: 0.790 AC: 4083 AN: 5170

South Asian (SAS) AF: 0.513 AC: 2461 AN: 4796

European-Finnish (FIN) AF: 0.576 AC: 6052 AN: 10504

Middle Eastern (MID) AF: 0.589 AC: 172 AN: 292

European-Non Finnish (NFE) AF: 0.598 AC: 40596 AN: 67934

Other (OTH) AF: 0.603 AC: 1271 AN: 2108

Alfa AF: 0.533 Hom.: 2550

Bravo AF: 0.600

Asia WGS AF: 0.630 AC: 2191 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	0.40
DANN	Benign	0.26
PhyloP100		-0.10
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: rs10517002; hg19: chr4-41264549;