Variant 1-26282310-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001389556.1(UBXN11):c.1552A>G(p.Ser518Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000017 in 1,466,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000072 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

UBXN11
NM_001389556.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.31

Variant links:

Genes affected

UBXN11 (HGNC:30600): (UBX domain protein 11) This gene encodes a protein with a divergent C-terminal UBX domain. The homologous protein in the rat interacts with members of the Rnd subfamily of Rho GTPases at the cell periphery through its C-terminal region. It also interacts with several heterotrimeric G proteins through their G-alpha subunits and promotes Rho GTPase activation. It is proposed to serve a bidirectional role in the promotion and inhibition of Rho activity through upstream signaling pathways. The 3' coding sequence of this gene contains a polymoprhic region of 24 nt tandem repeats. Several transcripts containing between 1.5 and five repeat units have been reported. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

UBXN11 links:

UBXN11 (HGNC:):

UBXN11 links:

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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=0.0529522).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBXN11	NM_001389556.1 linkuse as main transcript	c.1552A>G	p.Ser518Gly	missense_variant	15/15	ENST00000374222.6	NP_001376485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBXN11	ENST00000374222.6 linkuse as main transcript	c.1552A>G	p.Ser518Gly	missense_variant	15/15	5	NM_001389556.1	ENSP00000363339.1		Q5T124-1

Frequencies

GnomAD3 genomes

AF:

0.00000720

AC:

AN:

138944

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000746

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000201

AC:

AN:

149576

Hom.:

AF XY:

0.0000121

AC XY:

AN XY:

82668

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000643

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:

0.0000271

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000181

AC:

AN:

1327894

Hom.:

Cov.:

AF XY:

0.0000185

AC XY:

AN XY:

649552

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:

0.0000211

Gnomad4 OTH exome

AF:

0.0000370

GnomAD4 genome

AF:

0.00000720

AC:

AN:

138944

Hom.:

Cov.:

AF XY:

0.0000149

AC XY:

AN XY:

66986

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000746

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000936

Hom.:

ExAC

AF:

0.0000252

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

Aug 14, 2024

The c.1552A>G (p.S518G) alteration is located in exon 16 (coding exon 14) of the UBXN11 gene. This alteration results from a A to G substitution at nucleotide position 1552, causing the serine (S) at amino acid position 518 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

Benign

0.067

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.21

DANN

Benign

0.77

DEOGEN2

Benign

0.0054

.;T;.;T;.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.20

T;T;.;.;T;T

M_CAP

Benign

0.0020

MetaRNN

Benign

0.053

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;.;.;N;.;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.16

N;N;N;N;N;N

REVEL

Benign

0.019

Sift

Pathogenic

0.0

D;D;D;D;D;D

Sift4G

Benign

0.067

T;T;T;T;T;T

Polyphen

0.0010

B;.;B;B;B;B

Vest4

0.13

MutPred

0.20

.;.;.;Loss of phosphorylation at S518 (P = 6e-04);.;Loss of phosphorylation at S518 (P = 6e-04);

MVP

0.061

MPC

0.16

ClinPred

0.16

GERP RS

-5.0

Varity_R

0.088

gMVP

0.20

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