8-58411402-G-C

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001077619.2(UBXN2B):c.17G>C(p.Gly6Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000489 in 1,268,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G6V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

UBXN2B
NM_001077619.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.539

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.045086324).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBXN2B	NM_001077619.2 link	c.17G>C	p.Gly6Ala	missense_variant	Exon 1 of 8	ENST00000399598.7	NP_001071087.1	Q14CS0
UBXN2B	NM_001363181.1 link	c.17G>C	p.Gly6Ala	missense_variant	Exon 1 of 7		NP_001350110.1
UBXN2B	NM_001330535.2 link	c.17G>C	p.Gly6Ala	missense_variant	Exon 1 of 6		NP_001317464.1	Q14CS0E5RJ36
UBXN2B	NR_156456.1 link	n.42G>C		non_coding_transcript_exon_variant	Exon 1 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
UBXN2B	ENST00000399598.7 link	c.17G>C	p.Gly6Ala	missense_variant	Exon 1 of 8	1	NM_001077619.2	ENSP00000382507.2	Q14CS0
UBXN2B	ENST00000520732.5 link	n.17G>C		non_coding_transcript_exon_variant	Exon 1 of 6	3		ENSP00000427759.1	E5RGJ4
UBXN2B	ENST00000522978.1 link	n.44G>C		non_coding_transcript_exon_variant	Exon 1 of 7	3
UBXN2B	ENST00000523409.5 link	n.17G>C		non_coding_transcript_exon_variant	Exon 1 of 9	5		ENSP00000428314.1	E5RJ36

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000510

AC:

AN:

1116562

Hom.:

Cov.:

AF XY:

0.0000545

AC XY:

AN XY:

532254

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:

0.0000599

Gnomad4 OTH exome

AF:

0.0000224

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152272

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 08, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.17G>C (p.G6A) alteration is located in exon 1 (coding exon 1) of the UBXN2B gene. This alteration results from a G to C substitution at nucleotide position 17, causing the glycine (G) at amino acid position 6 to be replaced by an alanine (A). 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

0.083

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.64

DEOGEN2

Benign

0.011

T;.

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.028

MetaRNN

Benign

0.045

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

N;.

PrimateAI

Uncertain

0.64

PROVEAN

Benign

0.27

N;.

REVEL

Benign

0.058

Sift

Benign

1.0

T;.

Sift4G

Benign

0.45

T;.

Polyphen

0.0040

B;.

Vest4

0.10

MutPred

0.19

Loss of glycosylation at P9 (P = 0.2483);Loss of glycosylation at P9 (P = 0.2483);

MVP

0.18

MPC

0.088

ClinPred

0.073

GERP RS

3.2

Varity_R

0.055

gMVP

0.34

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