rs9321

Variant names:

• chr4-41256961-C-T
• rs9321
• NM_004181.5:c.-16C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-41256961-C-T
• chr4-41256961-C-A
• chr4-41256961-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004181.5(UCHL1):​c.-16C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0948 in 1,613,892 control chromosomes in the GnomAD database, including 7,986 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (874 hom., cov: 33)
  • Exomes 𝑓: 0.094 (7112 hom.)
• Consequence: UCHL1 NM_004181.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.53
• Publications: 13 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-DT (HGNC:40600): (UCHL1 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 4-41256961-C-T is Benign according to our data. Variant chr4-41256961-C-T is described in ClinVar as Benign. ClinVar VariationId is 348767.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004181.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UCHL1	NM_004181.5	MANE Select	c.-16C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	NP_004172.2
	UCHL1	NM_004181.5	MANE Select	c.-16C>T		5_prime_UTR	Exon 1 of 9	NP_004172.2
	UCHL1-DT	NR_102709.1		n.-234G>A		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UCHL1	ENST00000284440.9	TSL:1 MANE Select	c.-16C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	ENSP00000284440.4	P09936-1
	UCHL1	ENST00000284440.9	TSL:1 MANE Select	c.-16C>T		5_prime_UTR	Exon 1 of 9	ENSP00000284440.4	P09936-1
	UCHL1	ENST00000512788.1	TSL:3	c.-16C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	ENSP00000423623.1	D6R956

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15396 AN: 152130 Hom.: 872 Cov.: 33

Gnomad AFR AF: 0.0804

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.0809

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0917

Gnomad OTH AF: 0.0939

GnomAD2 exomes AF: 0.113 AC: 28397 AN: 250904 AF XY: 0.109

Gnomad AFR exome AF: 0.0819

Gnomad AMR exome AF: 0.146

Gnomad ASJ exome AF: 0.109

Gnomad EAS exome AF: 0.155

Gnomad FIN exome AF: 0.208

Gnomad NFE exome AF: 0.0919

Gnomad OTH exome AF: 0.107

GnomAD4 exome AF: 0.0941 AC: 137534 AN: 1461642 Hom.: 7112 Cov.: 32 AF XY: 0.0931 AC XY: 67667 AN XY: 727138

African (AFR) AF: 0.0802 AC: 2684 AN: 33480

American (AMR) AF: 0.141 AC: 6325 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 2812 AN: 26130

East Asian (EAS) AF: 0.148 AC: 5887 AN: 39696

South Asian (SAS) AF: 0.0831 AC: 7168 AN: 86248

European-Finnish (FIN) AF: 0.201 AC: 10734 AN: 53382

Middle Eastern (MID) AF: 0.0815 AC: 468 AN: 5740

European-Non Finnish (NFE) AF: 0.0860 AC: 95629 AN: 1111874

Other (OTH) AF: 0.0965 AC: 5827 AN: 60384

GnomAD4 genome AF: 0.101 AC: 15400 AN: 152250 Hom.: 874 Cov.: 33 AF XY: 0.107 AC XY: 7966 AN XY: 74424

African (AFR) AF: 0.0801 AC: 3331 AN: 41568

American (AMR) AF: 0.108 AC: 1647 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 377 AN: 3470

East Asian (EAS) AF: 0.153 AC: 787 AN: 5160

South Asian (SAS) AF: 0.0815 AC: 394 AN: 4832

European-Finnish (FIN) AF: 0.212 AC: 2246 AN: 10582

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0917 AC: 6238 AN: 68012

Other (OTH) AF: 0.0934 AC: 197 AN: 2110

Alfa AF: 0.0878 Hom.: 1069

Bravo AF: 0.0952

Asia WGS AF: 0.106 AC: 367 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Parkinson disease 5, autosomal dominant, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.041
DANN	Benign	0.83
PhyloP100		-1.5
PromoterAI		-0.032	Neutral
Mutation Taster		=300/0	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: rs9321; hg19: chr4-41258978; COSMIC: COSV52651008; COSMIC: COSV52651008;