chr17-48908673-G-C

Position:

• chr17-48908673-G-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_023079.5(UBE2Z):​c.170G>C​(p.Gly57Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,074,460 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: UBE2Z NM_023079.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.42

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0999403).
• BS2: High AC in GnomAdExome4 at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE2Z	NM_023079.5	c.170G>C	p.Gly57Ala	missense_variant	1/7	ENST00000360943.10	NP_075567.2
LOC105371814	NR_135674.1	n.45+266C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE2Z	ENST00000360943.10	c.170G>C	p.Gly57Ala	missense_variant	1/7	1	NM_023079.5	ENSP00000354201.5
UBE2Z	ENST00000508468.2	c.170G>C	p.Gly57Ala	missense_variant	1/3	3		ENSP00000424543.1
SUMO2P17	ENST00000508743.1	n.45+266C>G		intron_variant		3
UBE2Z	ENST00000506498.5	n.-44G>C		upstream_gene_variant		4		ENSP00000425398.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.0000186 AC: 20 AN: 1074460 Hom.: 0 Cov.: 31 AF XY: 0.0000157 AC XY: 8 AN XY: 510730

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000129

Gnomad4 ASJ exome AF: 0.0000751

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000175

Gnomad4 OTH exome AF: 0.0000472

GnomAD4 genome Cov.: 30

Bravo AF: 0.00000378

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 24, 2023

The c.170G>C (p.G57A) 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 170, causing the glycine (G) at amino acid position 57 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	0.071
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Benign	0.030	T;.
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.45	T;T
M_CAP	Pathogenic	0.80	D
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	0.11	N;N
REVEL	Benign	0.066
Sift	Benign	0.58	T;D
Sift4G	Benign	0.84	T;T
Polyphen		0.019	B;.
Vest4		0.12
MutPred		0.20		Loss of glycosylation at P58 (P = 0.1263);Loss of glycosylation at P58 (P = 0.1263);
MVP		0.18
MPC		1.4
ClinPred		0.093	T
GERP RS		1.4
Varity_R		0.070
gMVP		0.30

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: rs1210254404; hg19: chr17-46986035;