Genetic Variant NM_181713.4:c.56G>T (chr2-23971290-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_181713.4(UBXN2A):c.56G>T(p.Gly19Val) variant causes a missense change. The variant allele was found at a frequency of 0.000397 in 1,564,280 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 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00041 ( 0 hom. )

Consequence

UBXN2A
NM_181713.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.43

Publications

3 publications found

Variant links:

Genes affected

UBXN2A (HGNC:27265): (UBX domain protein 2A) Predicted to enable ubiquitin binding activity. Predicted to be involved in several processes, including autophagosome assembly; nuclear membrane reassembly; and proteasome-mediated ubiquitin-dependent protein catabolic process. Predicted to act upstream of or within cellular response to leukemia inhibitory factor; regulation of gene expression; and regulation of protein metabolic process. Predicted to be located in cis-Golgi network and endoplasmic reticulum. Predicted to be active in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

UBXN2A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0838936).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181713.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBXN2A	NM_181713.4	MANE Select	c.56G>T	p.Gly19Val	missense	Exon 3 of 7	NP_859064.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBXN2A	ENST00000309033.5	TSL:1 MANE Select	c.56G>T	p.Gly19Val	missense	Exon 3 of 7	ENSP00000312107.4	P68543-1
UBXN2A	ENST00000446425.2	TSL:1	n.518G>T		non_coding_transcript_exon	Exon 4 of 8
UBXN2A	ENST00000404924.5	TSL:2	c.56G>T	p.Gly19Val	missense	Exon 4 of 8	ENSP00000385525.1	P68543-1

Frequencies

GnomAD3 genomes

AF:

0.000283

AC:

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000259

AC:

AN:

246704

AF XY:

0.000263

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00170

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000390

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000409

AC:

578

AN:

1412174

Hom.:

Cov.:

AF XY:

0.000392

AC XY:

272

AN XY:

694128

show subpopulations

African (AFR)

AF:

0.0000610

AC:

AN:

32766

American (AMR)

AF:

0.0000694

AC:

AN:

43256

Ashkenazi Jewish (ASJ)

AF:

0.00166

AC:

AN:

25270

East Asian (EAS)

AF:

0.00

AC:

AN:

38648

South Asian (SAS)

AF:

0.0000127

AC:

AN:

78744

European-Finnish (FIN)

AF:

0.0000191

AC:

AN:

52374

Middle Eastern (MID)

AF:

0.000179

AC:

AN:

5582

European-Non Finnish (NFE)

AF:

0.000471

AC:

508

AN:

1077418

Other (OTH)

AF:

0.000344

AC:

AN:

58116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

114

143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

110

<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

AF:

0.000283

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41438

American (AMR)

AF:

0.00

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00260

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000426

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000460

Hom.:

Bravo

AF:

0.000264

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000255

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

0.083

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.076

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.75

M_CAP

Benign

0.014

MetaRNN

Benign

0.084

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.7

PhyloP100

4.4

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.11

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.037

Polyphen

0.99

Vest4

0.38

MVP

0.61

MPC

0.47

ClinPred

0.17

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.51

Mutation Taster

=77/23

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over