Variant 17-48922935-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_023079.5(UBE2Z):c.892C>A(p.Gln298Lys) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,456,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

UBE2Z
NM_023079.5 missense, splice_region

Scores

Splicing: ADA: 0.9390

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.43

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:

UBE2Z (HGNC:):

UBE2Z links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.33231035).

BS2

High AC in GnomAdExome4 at 22 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE2Z	NM_023079.5 linkuse as main transcript	c.892C>A	p.Gln298Lys	missense_variant, splice_region_variant	6/7	ENST00000360943.10	NP_075567.2	Q9H832-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE2Z	ENST00000360943.10 linkuse as main transcript	c.892C>A	p.Gln298Lys	missense_variant, splice_region_variant	6/7	1	NM_023079.5	ENSP00000354201.5		Q9H832-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000808

AC:

AN:

247404

Hom.:

AF XY:

0.00000748

AC XY:

AN XY:

133608

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000894

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1456950

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

724280

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:

0.0000198

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

Oct 26, 2022

The c.892C>A (p.Q298K) alteration is located in exon 6 (coding exon 6) of the UBE2Z gene. This alteration results from a C to A substitution at nucleotide position 892, causing the glutamine (Q) at amino acid position 298 to be replaced by a lysine (K). 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

0.74

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.056

T;T

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.92

D;T

M_CAP

Benign

0.040

MetaRNN

Benign

0.33

T;T

MetaSVM

Benign

-0.65

MutationAssessor

Benign

1.8

L;.

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.6

N;.

REVEL

Uncertain

0.34

Sift

Benign

0.10

T;.

Sift4G

Benign

0.25

T;D

Polyphen

0.085

B;.

Vest4

0.72

MutPred

0.40

Gain of ubiquitination at Q298 (P = 0.0101);.;

MVP

0.81

MPC

1.8

ClinPred

0.36

GERP RS

5.3

Varity_R

0.40

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.94

dbscSNV1_RF

Pathogenic

0.73

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