Variant 17-48908583-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_023079.5(UBE2Z):c.80T>G(p.Val27Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000021 in 1,239,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

UBE2Z
NM_023079.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.37

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:

SUMO2P17 (HGNC:):

SUMO2P17 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17650697).

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE2Z	NM_023079.5 linkuse as main transcript	c.80T>G	p.Val27Gly	missense_variant	1/7	ENST00000360943.10	NP_075567.2	Q9H832-1
LOC105371814	NR_135674.1 linkuse as main transcript	n.45+356A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
UBE2Z	ENST00000360943.10 linkuse as main transcript	c.80T>G	p.Val27Gly	missense_variant	1/7	1	NM_023079.5	ENSP00000354201.5	Q9H832-1
UBE2Z	ENST00000508468.2 linkuse as main transcript	c.80T>G	p.Val27Gly	missense_variant	1/3	3		ENSP00000424543.1	D6RB11
SUMO2P17	ENST00000508743.1 linkuse as main transcript	n.45+356A>C		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000397

AC:

AN:

150946

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000486

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000184

AC:

AN:

1088466

Hom.:

Cov.:

AF XY:

0.0000214

AC XY:

AN XY:

515074

show subpopulations

Gnomad4 AFR exome

AF:

0.000131

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000189

Gnomad4 SAS exome

AF:

0.0000511

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000119

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000397

AC:

AN:

150946

Hom.:

Cov.:

AF XY:

0.0000543

AC XY:

AN XY:

73664

show subpopulations

Gnomad4 AFR

AF:

0.0000486

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

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

Jun 21, 2022

The c.80T>G (p.V27G) alteration is located in exon 1 (coding exon 1) of the UBE2Z gene. This alteration results from a T to G substitution at nucleotide position 80, causing the valine (V) at amino acid position 27 to be replaced by a glycine (G). 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

0.064

BayesDel_addAF

Uncertain

0.031

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.060

T;.

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.32

T;T

M_CAP

Pathogenic

0.60

MetaRNN

Benign

0.18

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.34

N;.

PrimateAI

Pathogenic

0.96

PROVEAN

Benign

-0.60

N;N

REVEL

Uncertain

0.37

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.014

D;T

Polyphen

0.0

B;.

Vest4

0.41

MutPred

0.29

Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);

MVP

0.22

MPC

1.7

ClinPred

0.20

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.16

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