17-48908579-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_023079.5(UBE2Z):c.76G>T(p.Gly26Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000184 in 1,088,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: UBE2Z NM_023079.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.21

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2854115).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBE2Z	NM_023079.5	c.76G>T	p.Gly26Cys	missense_variant	1/7	ENST00000360943.10
LOC105371814	NR_135674.1	n.45+360C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBE2Z	ENST00000360943.10	c.76G>T	p.Gly26Cys	missense_variant	1/7	1	NM_023079.5	P1
	ENST00000508743.1	n.45+360C>A		intron_variant, non_coding_transcript_variant		3
UBE2Z	ENST00000508468.2	c.76G>T	p.Gly26Cys	missense_variant	1/3	3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000184 AC: 2 AN: 1088712 Hom.: 0 Cov.: 31 AF XY: 0.00000194 AC XY: 1 AN XY: 515132

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000239

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 Cov.: 30

Bravo AF: 0.0000302

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 03, 2023

The c.76G>T (p.G26C) alteration is located in exon 1 (coding exon 1) of the UBE2Z gene. This alteration results from a G to T substitution at nucleotide position 76, causing the glycine (G) at amino acid position 26 to be replaced by a cysteine (C). 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	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
Cadd	Uncertain	23
Dann	Uncertain	0.99
DEOGEN2	Benign	0.051	T;.
Eigen	Benign	-0.086
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.50	T;T
M_CAP	Pathogenic	0.64	D
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.0	N;.
MutationTaster	Benign	0.92	N
PrimateAI	Pathogenic	0.96	D
PROVEAN	Benign	-0.56	N;N
REVEL	Benign	0.28
Sift	Benign	0.095	T;D
Sift4G	Benign	0.067	T;T
Polyphen		0.99	D;.
Vest4		0.36
MutPred		0.36		Loss of phosphorylation at S23 (P = 0.0917);Loss of phosphorylation at S23 (P = 0.0917);
MVP		0.14
MPC		1.4
ClinPred		0.86	D
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.17
gMVP		0.50

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

Other links and lift over

dbSNP: rs1006082865; hg19: chr17-46985941;