2-238016619-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_080678.3(UBE2F):c.268G>A(p.Ala90Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

UBE2F
NM_080678.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.48

Variant links:

Genes affected

UBE2F (HGNC:12480): (ubiquitin conjugating enzyme E2 F (putative)) Enables NEDD8 conjugating enzyme activity. Involved in protein neddylation. Predicted to be located in cytosol. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

UBE2F links:

UBE2F-SCLY (HGNC:48339): (UBE2F-SCLY readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring UBE2F (ubiquitin-conjugating enzyme E2F) and SCLY (selenocysteine lyase) genes on chromosome 2. The read-through transcript is a candidate for non-sense mediated mRNA decay (NMD), and is unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

UBE2F-SCLY links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.41258898).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2F	NM_080678.3 link	c.268G>A	p.Ala90Thr	missense_variant	Exon 5 of 10	ENST00000272930.9	NP_542409.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2F	ENST00000272930.9 link	c.268G>A	p.Ala90Thr	missense_variant	Exon 5 of 10	1	NM_080678.3	ENSP00000272930.4		Q969M7-1
UBE2F-SCLY	ENST00000449191.1 link	n.268G>A		non_coding_transcript_exon_variant	Exon 5 of 11	3		ENSP00000456827.1		H3BSR4

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152010

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250780

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135552

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461392

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727002

show subpopulations

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:

0.00000720

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000658

AC:

AN:

152010

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 01, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.268G>A (p.A90T) alteration is located in exon 5 (coding exon 4) of the UBE2F gene. This alteration results from a G to A substitution at nucleotide position 268, causing the alanine (A) at amino acid position 90 to be replaced by a threonine (T). 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

0.19

BayesDel_addAF

Benign

-0.019

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.059

T;.;.;T;.;.;.;T;T;T

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

.;D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.032

MetaRNN

Benign

0.41

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.38

MutationAssessor

Benign

-0.38

N;.;.;.;N;.;.;.;N;.

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.67

N;N;N;N;N;N;N;N;.;N

REVEL

Uncertain

0.33

Sift

Benign

0.23

T;T;T;T;T;T;T;T;.;T

Sift4G

Benign

0.44

T;T;T;T;T;T;T;T;T;T

Polyphen

0.97

D;D;.;.;.;.;.;.;D;.

Vest4

0.60

MutPred

0.36

Gain of phosphorylation at A90 (P = 0.0555);.;.;.;Gain of phosphorylation at A90 (P = 0.0555);.;.;Gain of phosphorylation at A90 (P = 0.0555);Gain of phosphorylation at A90 (P = 0.0555);.;

MVP

0.52

MPC

1.5

ClinPred

0.82

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over