Variant 2-135741951-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_014607.4(UBXN4):c.22A>G(p.Ile8Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,052 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: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

UBXN4
NM_014607.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.15

Variant links:

Genes affected

UBXN4 (HGNC:14860): (UBX domain protein 4) UBXD2 is an integral membrane protein of the endoplasmic reticulum (ER) that binds valosin-containing protein (VCP; MIM 601023) and promotes ER-associated protein degradation (ERAD) (Liang et al., 2006 [PubMed 16968747]).[supplied by OMIM, Mar 2008]

UBXN4 links:

LOC107985946 (HGNC:):

LOC107985946 links:

Genome browser will be placed here

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=0.16456255).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBXN4	NM_014607.4 linkuse as main transcript	c.22A>G	p.Ile8Val	missense_variant	1/13	ENST00000272638.14
LOC107985946	NR_163478.1 linkuse as main transcript	n.694T>C		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
UBXN4	ENST00000272638.14 linkuse as main transcript	c.22A>G	p.Ile8Val	missense_variant	1/13	1	NM_014607.4	P1
UBXN4	ENST00000415164.5 linkuse as main transcript	c.22A>G	p.Ile8Val	missense_variant	1/5	4
UBXN4	ENST00000416538.5 linkuse as main transcript	c.22A>G	p.Ile8Val	missense_variant, NMD_transcript_variant	1/5	5
UBXN4	ENST00000426921.5 linkuse as main transcript	c.22A>G	p.Ile8Val	missense_variant, NMD_transcript_variant	1/4	4

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152202

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000411

AC:

AN:

243310

Hom.:

AF XY:

0.00000752

AC XY:

AN XY:

133010

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:

0.00000913

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1460850

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726792

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:

0.0000188

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 13, 2022

The c.22A>G (p.I8V) alteration is located in exon 1 (coding exon 1) of the UBXN4 gene. This alteration results from a A to G substitution at nucleotide position 22, causing the isoleucine (I) at amino acid position 8 to be replaced by a valine (V). 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

0.19

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

Cadd

Uncertain

Dann

Benign

0.97

DEOGEN2

Benign

0.021

T;.

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.72

N;N

REVEL

Benign

0.16

Sift

Benign

0.053

T;T

Sift4G

Benign

0.15

T;T

Polyphen

0.0010

B;.

Vest4

0.23

MutPred

0.46

Gain of disorder (P = 0.1769);Gain of disorder (P = 0.1769);

MVP

0.23

MPC

0.28

ClinPred

0.25

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.090

gMVP

0.73

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