1-193026083-C-T

Variant names:

• chr1-193026083-C-T
• rs9427573
• NM_001199261.3:c.629+2002G>A

Variant summary

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

The NM_001199261.3(UCHL5):​c.629+2002G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0207 in 133,136 control chromosomes in the GnomAD database, including 89 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 0.021 (89 hom., cov: 29)
• Consequence: UCHL5 NM_001199261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.439
• Publications: 7 publications found

Genes affected

UCHL5 (HGNC:19678): (ubiquitin C-terminal hydrolase L5) Enables endopeptidase inhibitor activity; proteasome binding activity; and thiol-dependent deubiquitinase. Involved in negative regulation of proteasomal ubiquitin-dependent protein catabolic process; positive regulation of smoothened signaling pathway; and protein deubiquitination. Located in cytosol; nucleolus; and nucleoplasm. Colocalizes with Ino80 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UCHL5	NM_001199261.3	c.629+2002G>A		intron_variant	Intron 7 of 10	ENST00000367454.6	NP_001186190.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UCHL5	ENST00000367454.6	c.629+2002G>A		intron_variant	Intron 7 of 10	1	NM_001199261.3	ENSP00000356424.1

Frequencies

GnomAD3 genomes AF: 0.0206 AC: 2746 AN: 133094 Hom.: 88 Cov.: 29

Gnomad AFR AF: 0.0717

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00899

Gnomad ASJ AF: 0.00514

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000240

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00806

Gnomad NFE AF: 0.000347

Gnomad OTH AF: 0.0169

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

GnomAD4 genome AF: 0.0207 AC: 2755 AN: 133136 Hom.: 89 Cov.: 29 AF XY: 0.0202 AC XY: 1282 AN XY: 63396

African (AFR) AF: 0.0719 AC: 2569 AN: 35754

American (AMR) AF: 0.00898 AC: 114 AN: 12692

Ashkenazi Jewish (ASJ) AF: 0.00514 AC: 17 AN: 3306

East Asian (EAS) AF: 0.00 AC: 0 AN: 4556

South Asian (SAS) AF: 0.000241 AC: 1 AN: 4150

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6458

Middle Eastern (MID) AF: 0.00885 AC: 2 AN: 226

European-Non Finnish (NFE) AF: 0.000347 AC: 22 AN: 63334

Other (OTH) AF: 0.0168 AC: 30 AN: 1782

Alfa AF: 0.00778 Hom.: 87

Bravo AF: 0.0223

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.75
DANN	Benign	0.63
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism

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: rs9427573; hg19: chr1-192995213;