chr1-193026083-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001199261.3(UCHL5):​c.629+2002G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.000045 (0 hom., cov: 29)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0000451 AC: 6 AN: 133084 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000560

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000219

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000155

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000316

Gnomad OTH AF: 0.00

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000451 AC: 6 AN: 133126 Hom.: 0 Cov.: 29 AF XY: 0.0000473 AC XY: 3 AN XY: 63384

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000559 AC: 2 AN: 35768

American (AMR) AF: 0.00 AC: 0 AN: 12688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3304

East Asian (EAS) AF: 0.000219 AC: 1 AN: 4556

South Asian (SAS) AF: 0.00 AC: 0 AN: 4148

European-Finnish (FIN) AF: 0.000155 AC: 1 AN: 6452

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 226

European-Non Finnish (NFE) AF: 0.0000316 AC: 2 AN: 63324

Other (OTH) AF: 0.00 AC: 0 AN: 1782

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 87

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.58
DANN	Benign	0.46
PhyloP100		-0.44

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;