Genetic Variant UBXN2A:p.Ile192Phe (chr2-23984821-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_181713.4(UBXN2A):c.574A>T(p.Ile192Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,398,134 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

UBXN2A
NM_181713.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.287

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06587064).

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.574A>T	p.Ile192Phe	missense	Exon 6 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.574A>T	p.Ile192Phe	missense	Exon 6 of 7	ENSP00000312107.4	P68543-1
UBXN2A	ENST00000446425.2	TSL:1	n.1036A>T		non_coding_transcript_exon	Exon 7 of 8
UBXN2A	ENST00000404924.5	TSL:2	c.574A>T	p.Ile192Phe	missense	Exon 7 of 8	ENSP00000385525.1	P68543-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000534

AC:

AN:

187410

AF XY:

0.00000967

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000106

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1398134

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

694726

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28584

American (AMR)

AF:

0.00

AC:

AN:

26884

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24196

East Asian (EAS)

AF:

0.00

AC:

AN:

35180

South Asian (SAS)

AF:

0.00

AC:

AN:

74446

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52828

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5624

European-Non Finnish (NFE)

AF:

0.00000183

AC:

AN:

1092734

Other (OTH)

AF:

0.00

AC:

AN:

57658

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

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

0.10

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

7.9

(source)

DANN

Benign

0.39

DEOGEN2

Benign

0.046

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.83

M_CAP

Benign

0.0049

MetaRNN

Benign

0.066

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.90

PhyloP100

-0.29

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.50

REVEL

Benign

0.039

Sift

Benign

0.65

Sift4G

Uncertain

0.052

Polyphen

0.055

Vest4

0.15

MutPred

0.22

Loss of MoRF binding (P = 0.1076)

MVP

0.081

MPC

0.23

ClinPred

0.027

GERP RS

-7.7

Varity_R

0.027

gMVP

0.44

Mutation Taster

=86/14

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over