17-76391328-G-A

Position:

• chr17-76391328-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022066.4(UBE2O):​c.3494C>T​(p.Ala1165Val) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBE2O NM_022066.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.882

Genes affected

UBE2O (HGNC:29554): (ubiquitin conjugating enzyme E2 O) Enables ubiquitin conjugating enzyme activity and ubiquitin protein ligase activity. Involved in positive regulation of BMP signaling pathway; protein ubiquitination; and retrograde transport, endosome to Golgi. Located in cytoplasm and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060121).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE2O	NM_022066.4	c.3494C>T	p.Ala1165Val	missense_variant	18/18	ENST00000319380.12	NP_071349.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE2O	ENST00000319380.12	c.3494C>T	p.Ala1165Val	missense_variant	18/18	1	NM_022066.4	ENSP00000323687.6
UBE2O	ENST00000587127.1	c.2036C>T	p.Ala679Val	missense_variant	10/10	1		ENSP00000468498.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

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

Jun 29, 2023

The c.3494C>T (p.A1165V) alteration is located in exon 18 (coding exon 18) of the UBE2O gene. This alteration results from a C to T substitution at nucleotide position 3494, causing the alanine (A) at amino acid position 1165 to be replaced by a valine (V). 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	0.088
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	15
DANN	Benign	0.91
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.14
Sift	Benign	0.26	T
Sift4G	Benign	0.24	T
Polyphen		0.0040	B
Vest4		0.049
MutPred		0.14		Loss of glycosylation at P1163 (P = 0.088);
MVP		0.20
MPC		0.60
ClinPred		0.061	T
GERP RS		3.7
Varity_R		0.032
gMVP		0.19

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: chr17-74387409;