17-48908670-G-C

Position:

• chr17-48908670-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_023079.5(UBE2Z):​c.167G>C​(p.Gly56Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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)
• Consequence: UBE2Z NM_023079.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.68

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]

SUMO2P17 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15795141).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE2Z	NM_023079.5	c.167G>C	p.Gly56Ala	missense_variant	1/7	ENST00000360943.10	NP_075567.2
LOC105371814	NR_135674.1	n.45+269C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE2Z	ENST00000360943.10	c.167G>C	p.Gly56Ala	missense_variant	1/7	1	NM_023079.5	ENSP00000354201.5
UBE2Z	ENST00000508468.2	c.167G>C	p.Gly56Ala	missense_variant	1/3	3		ENSP00000424543.1
SUMO2P17	ENST00000508743.1	n.45+269C>G		intron_variant		3
UBE2Z	ENST00000506498.5	n.-47G>C		upstream_gene_variant		4		ENSP00000425398.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

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

Apr 19, 2024

The c.167G>C (p.G56A) alteration is located in exon 1 (coding exon 1) of the UBE2Z gene. This alteration results from a G to C substitution at nucleotide position 167, causing the glycine (G) at amino acid position 56 to be replaced by an alanine (A). 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	0.065
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	21
DANN	Benign	0.81
DEOGEN2	Benign	0.046	T;.
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.58	T;T
M_CAP	Pathogenic	0.88	D
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	N;.
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.20	N;N
REVEL	Benign	0.13
Sift	Benign	1.0	T;T
Sift4G	Benign	0.97	T;T
Polyphen		0.24	B;.
Vest4		0.16
MutPred		0.13		Loss of catalytic residue at A55 (P = 0.1641);Loss of catalytic residue at A55 (P = 0.1641);
MVP		0.50
MPC		1.4
ClinPred		0.26	T
GERP RS		2.5
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		3.5
Varity_R		0.088
gMVP		0.32

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: chr17-46986032;