17-48921262-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_023079.5(UBE2Z):c.793G>A(p.Glu265Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,552 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: UBE2Z NM_023079.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.66

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBE2Z	NM_023079.5	c.793G>A	p.Glu265Lys	missense_variant	5/7	ENST00000360943.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBE2Z	ENST00000360943.10	c.793G>A	p.Glu265Lys	missense_variant	5/7	1	NM_023079.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458552 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 725186

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000226

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.: 32

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

Oct 05, 2021

The c.793G>A (p.E265K) alteration is located in exon 5 (coding exon 5) of the UBE2Z gene. This alteration results from a G to A substitution at nucleotide position 793, causing the glutamic acid (E) at amino acid position 265 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	Uncertain	0.48
BayesDel_addAF	Uncertain	0.087	D
BayesDel_noAF	Benign	-0.11
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.24	T;.;T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.43	T;T;T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.7	L;.;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-2.4	N;N;.
REVEL	Benign	0.23
Sift	Benign	0.057	T;D;.
Sift4G	Benign	0.14	T;T;T
Polyphen		0.014	B;.;.
Vest4		0.48
MutPred		0.49		Gain of methylation at E265 (P = 0.0153);.;.;
MVP		0.54
MPC		1.5
ClinPred		0.89	D
GERP RS		6.0
Varity_R		0.48
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1460213314; hg19: chr17-46998624;