Variant 2-135779056-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014607.4(UBXN4):c.1162A>G(p.Ser388Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,122 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

UBXN4
NM_014607.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.33

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:

UBXN4 (HGNC:):

UBXN4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBXN4	NM_014607.4 linkuse as main transcript	c.1162A>G	p.Ser388Gly	missense_variant	11/13	ENST00000272638.14	NP_055422.1	Q92575

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
UBXN4	ENST00000272638.14 linkuse as main transcript	c.1162A>G	p.Ser388Gly	missense_variant	11/13	1	NM_014607.4	ENSP00000272638.9	Q92575
UBXN4	ENST00000471246.1 linkuse as main transcript	n.313A>G		non_coding_transcript_exon_variant	3/4	3
UBXN4	ENST00000490163.5 linkuse as main transcript	n.861A>G		non_coding_transcript_exon_variant	7/9	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000201

AC:

AN:

249088

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135174

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000146

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461122

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726850

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000202

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000189

ExAC

AF:

0.00000828

AC:

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

Nov 10, 2024

The c.1162A>G (p.S388G) alteration is located in exon 11 (coding exon 11) of the UBXN4 gene. This alteration results from a A to G substitution at nucleotide position 1162, causing the serine (S) at amino acid position 388 to be replaced by a glycine (G). 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

Uncertain

0.53

BayesDel_addAF

Uncertain

0.032

BayesDel_noAF

Uncertain

0.030

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.49

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.78

M_CAP

Benign

0.040

MetaRNN

Uncertain

0.65

MetaSVM

Benign

-0.60

MutationAssessor

Uncertain

2.6

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-2.8

REVEL

Uncertain

0.32

Sift

Benign

0.11

Sift4G

Benign

0.099

Polyphen

0.094

Vest4

0.86

MutPred

0.65

Loss of phosphorylation at S388 (P = 0.0665);

MVP

0.35

MPC

0.58

ClinPred

0.76

GERP RS

5.1

Varity_R

0.36

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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