Variant 1-19076803-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_020765.3(UBR4):c.15424C>G(p.Leu5142Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,584 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

UBR4
NM_020765.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.43

Variant links:

Genes affected

UBR4 (HGNC:30313): (ubiquitin protein ligase E3 component n-recognin 4) The protein encoded by this gene is an E3 ubiquitin-protein ligase that interacts with the retinoblastoma-associated protein in the nucleus and with calcium-bound calmodulin in the cytoplasm. The encoded protein appears to be a cytoskeletal component in the cytoplasm and part of the chromatin scaffold in the nucleus. In addition, this protein is a target of the human papillomavirus type 16 E7 oncoprotein. [provided by RefSeq, Aug 2010]

UBR4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, UBR4

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBR4	NM_020765.3 linkuse as main transcript	c.15424C>G	p.Leu5142Val	missense_variant	105/106	ENST00000375254.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBR4	ENST00000375254.8 linkuse as main transcript	c.15424C>G	p.Leu5142Val	missense_variant	105/106	1	NM_020765.3	P1	Q5T4S7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251044

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135730

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461584

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

The c.15424C>G (p.L5142V) alteration is located in exon 105 (coding exon 105) of the UBR4 gene. This alteration results from a C to G substitution at nucleotide position 15424, causing the leucine (L) at amino acid position 5142 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

Benign

0.27

BayesDel_addAF

Benign

-0.050

BayesDel_noAF

Benign

-0.14

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.33

T;.;.

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.86

D;D;D

M_CAP

Benign

0.0091

MetaRNN

Uncertain

0.60

D;D;D

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.6

L;.;.

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-2.4

N;D;D

REVEL

Benign

0.16

Sift

Uncertain

0.026

D;D;D

Polyphen

0.98

D;.;.

Vest4

0.67

MutPred

0.37

Gain of methylation at K5143 (P = 0.0325);.;.;

MVP

0.12

MPC

0.68

ClinPred

0.91

GERP RS

5.0

Varity_R

0.37

gMVP

0.53

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over