chr19-18573706-C-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_001033930.3(UBA52):c.148C>G(p.Leu50Val) variant causes a missense change. The variant allele was found at a frequency of 0.000015 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

UBA52
NM_001033930.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.84

Publications

0 publications found

Variant links:

Genes affected

UBA52 (HGNC:12458): (ubiquitin A-52 residue ribosomal protein fusion product 1) Ubiquitin is a highly conserved nuclear and cytoplasmic protein that has a major role in targeting cellular proteins for degradation by the 26S proteosome. It is also involved in the maintenance of chromatin structure, the regulation of gene expression, and the stress response. Ubiquitin is synthesized as a precursor protein consisting of either polyubiquitin chains or a single ubiquitin moiety fused to an unrelated protein. This gene encodes a fusion protein consisting of ubiquitin at the N terminus and ribosomal protein L40 at the C terminus, a C-terminal extension protein (CEP). Multiple processed pseudogenes derived from this gene are present in the genome. [provided by RefSeq, Jul 2008]

UBA52 links:

CRLF1 (HGNC:2364): (cytokine receptor like factor 1) This gene encodes a member of the cytokine type I receptor family. The protein forms a secreted complex with cardiotrophin-like cytokine factor 1 and acts on cells expressing ciliary neurotrophic factor receptors. The complex can promote survival of neuronal cells. Mutations in this gene result in Crisponi syndrome and cold-induced sweating syndrome. [provided by RefSeq, Oct 2009]

CRLF1 Gene-Disease associations (from GenCC):

Cold-induced sweating syndrome 1
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
cold-induced sweating syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
idiopathic achalasia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CRLF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.911

BS2

High AC in GnomAdExome4 at 22 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBA52	NM_001033930.3 link	c.148C>G	p.Leu50Val	missense_variant	Exon 3 of 5	ENST00000442744.7	NP_001029102.1	P62987Q3MIH3Q7Z4P3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBA52	ENST00000442744.7 link	c.148C>G	p.Leu50Val	missense_variant	Exon 3 of 5	1	NM_001033930.3	ENSP00000388107.1		P62987

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000119

AC:

AN:

251336

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000150

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000198

AC:

AN:

1112008

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.430

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 08, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.148C>G (p.L50V) alteration is located in exon 3 (coding exon 2) of the UBA52 gene. This alteration results from a C to G substitution at nucleotide position 148, causing the leucine (L) at amino acid position 50 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.36

BayesDel_noAF

Pathogenic

0.35

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.49

T;T;T;T;T;T;T;T;T;T;T;.;T

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.95

.;.;.;.;.;D;.;.;.;.;D;D;D

M_CAP

Pathogenic

0.44

MetaRNN

Pathogenic

0.91

D;D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Uncertain

0.067

MutationAssessor

Pathogenic

3.6

H;H;H;H;H;.;H;H;H;H;H;.;.

PhyloP100

3.8

PrimateAI

Pathogenic

0.89

PROVEAN

Uncertain

-2.9

.;D;.;D;.;.;.;.;.;.;.;.;.

REVEL

Pathogenic

0.68

Sift

Uncertain

0.0010

.;D;.;D;.;.;.;.;.;.;.;.;.

Sift4G

Pathogenic

0.0010

D;D;D;D;D;D;D;D;D;D;D;D;D

Polyphen

0.27

B;B;B;B;B;.;B;B;B;B;B;.;.

Vest4

0.88

MutPred

0.80

Loss of ubiquitination at K48 (P = 0.1037);Loss of ubiquitination at K48 (P = 0.1037);Loss of ubiquitination at K48 (P = 0.1037);Loss of ubiquitination at K48 (P = 0.1037);Loss of ubiquitination at K48 (P = 0.1037);Loss of ubiquitination at K48 (P = 0.1037);Loss of ubiquitination at K48 (P = 0.1037);Loss of ubiquitination at K48 (P = 0.1037);Loss of ubiquitination at K48 (P = 0.1037);Loss of ubiquitination at K48 (P = 0.1037);Loss of ubiquitination at K48 (P = 0.1037);.;.;

MVP

0.94

MPC

1.4

ClinPred

0.91

GERP RS

4.8

PromoterAI

-0.011

Neutral

(source)

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.9

Varity_R

0.93

gMVP

0.90

Mutation Taster

=27/73

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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chr19-18573706-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over