Variant 17-48908646-C-T 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.143C>T(p.Ala48Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000465 in 1,225,294 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: 0.000047 ( 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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2176556).

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.143C>T	p.Ala48Val	missense_variant	1/7	ENST00000360943.10	NP_075567.2	Q9H832-1
LOC105371814	NR_135674.1 linkuse as main transcript	n.45+293G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
UBE2Z	ENST00000360943.10 linkuse as main transcript	c.143C>T	p.Ala48Val	missense_variant	1/7	1	NM_023079.5	ENSP00000354201.5	Q9H832-1
UBE2Z	ENST00000508468.2 linkuse as main transcript	c.143C>T	p.Ala48Val	missense_variant	1/3	3		ENSP00000424543.1	D6RB11
SUMO2P17	ENST00000508743.1 linkuse as main transcript	n.45+293G>A		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000399

AC:

AN:

150192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000197

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000594

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000474

AC:

AN:

1074994

Hom.:

Cov.:

AF XY:

0.0000530

AC XY:

AN XY:

509560

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000547

Gnomad4 OTH exome

AF:

0.0000235

GnomAD4 genome

AF:

0.0000399

AC:

AN:

150300

Hom.:

Cov.:

AF XY:

0.0000681

AC XY:

AN XY:

73388

show subpopulations

Gnomad4 AFR

AF:

0.0000243

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000197

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000594

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

Sep 30, 2021

The c.143C>T (p.A48V) 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 143, causing the alanine (A) at amino acid position 48 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

0.20

BayesDel_addAF

Benign

-0.082

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.060

T;.

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.53

T;T

M_CAP

Pathogenic

0.74

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;.

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.20

N;N

REVEL

Benign

0.057

Sift

Uncertain

0.0060

D;T

Sift4G

Benign

0.72

T;T

Polyphen

0.0020

B;.

Vest4

0.22

MutPred

0.31

Loss of helix (P = 0.079);Loss of helix (P = 0.079);

MVP

0.12

MPC

1.3

ClinPred

0.10

GERP RS

1.8

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

3.5

Varity_R

0.096

gMVP

0.57

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