Genetic Variant UBXN2B:p.Asp37Glu (chr8-58416876-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001077619.2(UBXN2B):c.111T>A(p.Asp37Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.0000021 ( 0 hom. )

Consequence

UBXN2B
NM_001077619.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.557

Variant links:

Genes affected

UBXN2B (HGNC:27035): (UBX domain protein 2B) Predicted to enable ubiquitin binding activity. Involved in establishment of mitotic spindle orientation; negative regulation of protein localization to centrosome; and positive regulation of mitotic centrosome separation. Predicted to be located in Golgi apparatus; endoplasmic reticulum; and spindle pole centrosome. Predicted to be active in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

UBXN2B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12171596).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBXN2B	NM_001077619.2 link	c.111T>A	p.Asp37Glu	missense_variant	Exon 2 of 8	ENST00000399598.7	NP_001071087.1	Q14CS0
UBXN2B	NM_001363181.1 link	c.111T>A	p.Asp37Glu	missense_variant	Exon 2 of 7		NP_001350110.1
UBXN2B	NM_001330535.2 link	c.111T>A	p.Asp37Glu	missense_variant	Exon 2 of 6		NP_001317464.1	Q14CS0E5RJ36
UBXN2B	NR_156456.1 link	n.136T>A		non_coding_transcript_exon_variant	Exon 2 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBXN2B	ENST00000399598.7 link	c.111T>A	p.Asp37Glu	missense_variant	Exon 2 of 8	1	NM_001077619.2	ENSP00000382507.2		Q14CS0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249164

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135222

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460424

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726530

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:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 17, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.111T>A (p.D37E) alteration is located in exon 2 (coding exon 2) of the UBXN2B gene. This alteration results from a T to A substitution at nucleotide position 111, causing the aspartic acid (D) at amino acid position 37 to be replaced by a glutamic acid (E). 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

0.12

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.035

T;.

Eigen

Benign

0.0051

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.0065

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;.

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.2

N;.

REVEL

Benign

0.11

Sift

Benign

0.075

T;.

Sift4G

Benign

0.20

T;.

Polyphen

0.60

P;.

Vest4

0.25

MutPred

0.31

Loss of loop (P = 0.0112);Loss of loop (P = 0.0112);

MVP

0.42

MPC

0.084

ClinPred

0.33

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.067

gMVP

0.25

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

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