rs752414958

Variant names:

• chr13-75605747-A-C
• rs752414958
• NM_006002.5:c.628A>C

Your query was ambiguous. Multiple possible variants found:

• chr13-75605747-A-C
• chr13-75605747-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006002.5(UCHL3):​c.628A>C​(p.Lys210Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: UCHL3 NM_006002.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.75

Genes affected

UCHL3 (HGNC:12515): (ubiquitin C-terminal hydrolase L3) The protein encoded by this gene is a member of the deubiquitinating enzyme family. Members of this family are proteases that catalyze the removal of ubiquitin from polypeptides and are divided into five classes, depending on the mechanism of catalysis. This protein may hydrolyze the ubiquitinyl-N-epsilon amide bond of ubiquitinated proteins to regenerate ubiquitin for another catalytic cycle. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Aug 2012]

ENSG00000261553 (HGNC:):

LMO7-AS1 (HGNC:50277): (LMO7 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28592557).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UCHL3	NM_006002.5	c.628A>C	p.Lys210Gln	missense_variant	Exon 9 of 9	ENST00000377595.8	NP_005993.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UCHL3	ENST00000377595.8	c.628A>C	p.Lys210Gln	missense_variant	Exon 9 of 9	1	NM_006002.5	ENSP00000366819.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461710 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727156

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.012	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.17	.;T;.
Eigen	Benign	0.043
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	.;L;.
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.5	.;N;N
REVEL	Benign	0.082
Sift	Benign	0.34	.;T;T
Sift4G	Benign	0.45	T;T;T
Polyphen		0.096	.;B;.
Vest4		0.45
MutPred		0.45		.;Loss of methylation at K210 (P = 0.0012);.;
MVP		0.54
MPC		0.42
ClinPred		0.80	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.48
gMVP		0.77

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: rs752414958; hg19: chr13-76179883;