Variant 17-48908667-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_023079.5(UBE2Z):c.164C>T(p.Ala55Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000246 in 1,221,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 30)

Exomes 𝑓: 9.3e-7 ( 0 hom. )

Consequence

UBE2Z
NM_023079.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.241

Variant links:

Genes affected

UBE2Z (HGNC:25847): (ubiquitin conjugating enzyme E2 Z) This gene encodes an enzyme which ubiquitinates proteins which participate in signaling pathways and apoptosis. [provided by RefSeq, Feb 2012]

UBE2Z links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12691298).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBE2Z	NM_023079.5 linkuse as main transcript	c.164C>T	p.Ala55Val	missense_variant	1/7	ENST00000360943.10
LOC105371814	NR_135674.1 linkuse as main transcript	n.45+272G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBE2Z	ENST00000360943.10 linkuse as main transcript	c.164C>T	p.Ala55Val	missense_variant	1/7	1	NM_023079.5	P1	Q9H832-1
	ENST00000508743.1 linkuse as main transcript	n.45+272G>A		intron_variant, non_coding_transcript_variant		3
UBE2Z	ENST00000508468.2 linkuse as main transcript	c.164C>T	p.Ala55Val	missense_variant	1/3	3
UBE2Z	ENST00000506498.5 linkuse as main transcript			upstream_gene_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150730

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.34e-7

AC:

AN:

1071118

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

508408

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000130

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000133

AC:

AN:

150730

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73544

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000132

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

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

Dec 16, 2022

The c.164C>T (p.A55V) alteration is located in exon 1 (coding exon 1) of the UBE2Z gene. This alteration results from a C to T substitution at nucleotide position 164, causing the alanine (A) at amino acid position 55 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

0.11

BayesDel_addAF

Benign

-0.0031

BayesDel_noAF

Benign

-0.24

Cadd

Benign

Dann

Benign

0.97

DEOGEN2

Benign

0.045

T;.

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.53

T;T

M_CAP

Pathogenic

0.83

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.

MutationTaster

Benign

0.93

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.47

N;N

REVEL

Benign

0.067

Sift

Benign

0.11

T;T

Sift4G

Benign

0.18

T;T

Polyphen

0.012

B;.

Vest4

0.093

MutPred

0.20

Loss of relative solvent accessibility (P = 0.0186);Loss of relative solvent accessibility (P = 0.0186);

MVP

0.25

MPC

1.3

ClinPred

0.15

GERP RS

1.6

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

3.5

Varity_R

0.084

gMVP

0.36

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