4-41256999-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004181.5(UCHL1):c.23T>C(p.Ile8Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: UCHL1 NM_004181.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.46

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UCHL1	NM_004181.5	c.23T>C	p.Ile8Thr	missense_variant	1/9	ENST00000284440.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UCHL1	ENST00000284440.9	c.23T>C	p.Ile8Thr	missense_variant	1/9	1	NM_004181.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
Cadd	Uncertain	25
Dann	Uncertain	1.0
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.79	T;.;D;D;T
M_CAP	Benign	0.051	D
MetaRNN	Uncertain	0.63	D;D;D;D;D
MetaSVM	Benign	-0.37	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.19	N;N;N;N;N
REVEL	Uncertain	0.32
Sift	Benign	0.55	T;T;T;T;T
Sift4G	Uncertain	0.020	D;T;T;T;T
Polyphen		1.0	.;D;D;.;.
Vest4		0.65, 0.65, 0.64, 0.65
MutPred		0.57		Gain of disorder (P = 0.0196);Gain of disorder (P = 0.0196);Gain of disorder (P = 0.0196);Gain of disorder (P = 0.0196);Gain of disorder (P = 0.0196);
MVP		0.48
MPC		1.7
ClinPred		0.90	D
GERP RS		4.8
Varity_R		0.50
gMVP		0.52

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-41259016;