17-48908748-A-G

Variant summary

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

The NM_023079.5(UBE2Z):c.245A>G(p.His82Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UBE2Z NM_023079.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.45

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=0.28543282).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBE2Z	NM_023079.5	c.245A>G	p.His82Arg	missense_variant	1/7	ENST00000360943.10
LOC105371814	NR_135674.1	n.45+191T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBE2Z	ENST00000360943.10	c.245A>G	p.His82Arg	missense_variant	1/7	1	NM_023079.5	P1
	ENST00000508743.1	n.45+191T>C		intron_variant, non_coding_transcript_variant		3
UBE2Z	ENST00000508468.2	c.245A>G	p.His82Arg	missense_variant	1/3	3
UBE2Z	ENST00000506498.5	c.35A>G	p.His12Arg	missense_variant, NMD_transcript_variant	1/7	4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1341334 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 662166

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

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

Jul 25, 2023

The c.245A>G (p.H82R) alteration is located in exon 1 (coding exon 1) of the UBE2Z gene. This alteration results from a A to G substitution at nucleotide position 245, causing the histidine (H) at amino acid position 82 to be replaced by an arginine (R). 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	0.26
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
Cadd	Benign	21
Dann	Benign	0.95
DEOGEN2	Benign	0.048	T;.
Eigen	Benign	0.017
Eigen_PC	Benign	0.031
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.50	T;T
M_CAP	Pathogenic	0.95	D
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	0.34	N;.
MutationTaster	Benign	0.70	N
PrimateAI	Pathogenic	0.96	D
PROVEAN	Benign	-0.84	N;N
REVEL	Benign	0.13
Sift	Benign	0.11	T;T
Sift4G	Benign	0.79	T;T
Polyphen		0.82	P;.
Vest4		0.19
MutPred		0.26		Gain of disorder (P = 0.1147);Gain of disorder (P = 0.1147);
MVP		0.39
MPC		1.6
ClinPred		0.25	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.15
gMVP		0.20

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-46986110;