Genetic Variant UBXN2A:p.Ala55Thr (chr2-23971397-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_181713.4(UBXN2A):c.163G>A(p.Ala55Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,547,326 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: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000072 ( 0 hom. )

Consequence

UBXN2A
NM_181713.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.142

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02720359).

BP6

Variant 2-23971397-G-A is Benign according to our data. Variant chr2-23971397-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2376279.Status of the report is criteria_provided_single_submitter, 1 stars.

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.163G>A	p.Ala55Thr	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.163G>A	p.Ala55Thr	missense	Exon 3 of 7	ENSP00000312107.4	P68543-1
UBXN2A	ENST00000446425.2	TSL:1	n.625G>A		non_coding_transcript_exon	Exon 4 of 8
UBXN2A	ENST00000404924.5	TSL:2	c.163G>A	p.Ala55Thr	missense	Exon 4 of 8	ENSP00000385525.1	P68543-1

Frequencies

GnomAD3 genomes

AF:

0.0000921

AC:

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

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

GnomAD2 exomes

AF:

0.0000165

AC:

AN:

243124

AF XY:

0.0000228

show subpopulations

Gnomad AFR exome

AF:

0.0000621

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000268

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000717

AC:

AN:

1395242

Hom.:

Cov.:

AF XY:

0.00000729

AC XY:

AN XY:

685464

show subpopulations

African (AFR)

AF:

0.0000923

AC:

AN:

32494

American (AMR)

AF:

0.00

AC:

AN:

42114

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24800

East Asian (EAS)

AF:

0.00

AC:

AN:

38504

South Asian (SAS)

AF:

0.00

AC:

AN:

74818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51754

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5460

European-Non Finnish (NFE)

AF:

0.00000655

AC:

AN:

1068118

Other (OTH)

AF:

0.00

AC:

AN:

57180

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

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

AF:

0.0000921

AC:

AN:

152084

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.000314

AC:

AN:

41424

American (AMR)

AF:

0.00

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68002

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

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:

0.0000659

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.0000247

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

0.059

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.41

(source)

DANN

Benign

0.14

DEOGEN2

Benign

0.0059

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0025

LIST_S2

Benign

0.48

M_CAP

Benign

0.0023

MetaRNN

Benign

0.027

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.90

PhyloP100

-0.14

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.47

REVEL

Benign

0.043

Sift

Benign

0.96

Sift4G

Benign

0.87

Polyphen

0.0

Vest4

0.067

MVP

0.095

MPC

0.12

ClinPred

0.0073

GERP RS

0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.018

gMVP

0.14

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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