Genetic Variant UBOX5:p.Gly471Ser (chr20-3115311-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_014948.4(UBOX5):c.1411G>A(p.Gly471Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000823 in 1,458,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

UBOX5
NM_014948.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.33

Publications

1 publications found

Variant links:

Genes affected

UBOX5 (HGNC:17777): (U-box domain containing 5) This gene encodes a U-box domain containing protein. The encoded protein interacts with E2 enzymes and may play a role in the ubiquitination pathway. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

UBOX5 links:

UBOX5-AS1 (HGNC:44111): (UBOX5 antisense RNA 1)

UBOX5-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.031015664).

BP6

Variant 20-3115311-C-T is Benign according to our data. Variant chr20-3115311-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3812995.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014948.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBOX5	NM_014948.4	MANE Select	c.1411G>A	p.Gly471Ser	missense	Exon 4 of 5	NP_055763.1	O94941-1
UBOX5	NM_001267584.2		c.1411G>A	p.Gly471Ser	missense	Exon 4 of 5	NP_001254513.1
UBOX5	NM_199415.3		c.1256-4997G>A		intron	N/A	NP_955447.1	O94941-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBOX5	ENST00000217173.7	TSL:1 MANE Select	c.1411G>A	p.Gly471Ser	missense	Exon 4 of 5	ENSP00000217173.2	O94941-1
UBOX5	ENST00000348031.6	TSL:1	c.1256-4997G>A		intron	N/A	ENSP00000311726.3	O94941-2
UBOX5	ENST00000896614.1		c.1411G>A	p.Gly471Ser	missense	Exon 3 of 4	ENSP00000566673.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000811

AC:

AN:

246634

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000823

AC:

AN:

1458452

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

725520

show subpopulations

African (AFR)

AF:

0.0000601

AC:

AN:

33290

American (AMR)

AF:

0.00

AC:

AN:

44156

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25912

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39436

South Asian (SAS)

AF:

0.00

AC:

AN:

85780

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53356

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.00000720

AC:

AN:

1110582

Other (OTH)

AF:

0.0000166

AC:

AN:

60246

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000280

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.79

CADD

Benign

3.0

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.024

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.34

M_CAP

Benign

0.0052

MetaRNN

Benign

0.031

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.69

PhyloP100

-1.3

PrimateAI

Benign

0.29

PROVEAN

Benign

0.66

REVEL

Benign

0.049

Sift

Benign

0.58

Sift4G

Benign

0.82

Polyphen

0.0020

Vest4

0.099

MutPred

0.14

Gain of relative solvent accessibility (P = 0.0249)

MVP

0.20

MPC

0.26

ClinPred

0.022

GERP RS

-5.8

Varity_R

0.033

gMVP

0.18

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over