1-193026083-C-T

Position:

• chr1-193026083-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
UCHL5	NM_001199261.3	c.629+2002G>A		intron_variant		ENST00000367454.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UCHL5	ENST00000367454.6	c.629+2002G>A		intron_variant		1	NM_001199261.3	A1

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

Gnomad4 AFR AF: 0.0719

Gnomad4 AMR AF: 0.00898

Gnomad4 ASJ AF: 0.00514

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000241

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000347

Gnomad4 OTH AF: 0.0168

Alfa AF: 0.00198 Hom.: 11

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

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

LitVar

Other links and lift over

dbSNP: rs9427573; hg19: chr1-192995213;