Variant chr1-26282406-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001389556.1(UBXN11):c.1456T>G(p.Cys486Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000551 in 1,397,676 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000055 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

UBXN11
NM_001389556.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.01

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01684469).

BP6

Variant 1-26282406-A-C is Benign according to our data. Variant chr1-26282406-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3185907.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBXN11	NM_001389556.1 linkuse as main transcript	c.1456T>G	p.Cys486Gly	missense_variant	15/15	ENST00000374222.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBXN11	ENST00000374222.6 linkuse as main transcript	c.1456T>G	p.Cys486Gly	missense_variant	15/15	5	NM_001389556.1	A2	Q5T124-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

129054

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000910

Gnomad ASJ

AF:

0.000633

Gnomad EAS

AF:

0.000444

Gnomad SAS

AF:

0.000896

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00368

Gnomad NFE

AF:

0.0000468

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000123

AC:

AN:

219922

Hom.:

AF XY:

0.000158

AC XY:

AN XY:

120412

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000176

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000460

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000953

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000551

AC:

AN:

1397676

Hom.:

Cov.:

AF XY:

0.0000577

AC XY:

AN XY:

693470

show subpopulations

Gnomad4 AFR exome

AF:

0.0000320

Gnomad4 AMR exome

AF:

0.000184

Gnomad4 ASJ exome

AF:

0.000241

Gnomad4 EAS exome

AF:

0.0000409

Gnomad4 SAS exome

AF:

0.000253

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000285

Gnomad4 OTH exome

AF:

0.000141

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000124

AC:

AN:

129130

Hom.:

Cov.:

AF XY:

0.000129

AC XY:

AN XY:

62248

show subpopulations

Gnomad4 AFR

AF:

0.000150

Gnomad4 AMR

AF:

0.0000909

Gnomad4 ASJ

AF:

0.000633

Gnomad4 EAS

AF:

0.000446

Gnomad4 SAS

AF:

0.000896

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000468

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000481

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.0040

DANN

Benign

0.18

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.43

T;T;.;.;T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.017

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.44

N;N;N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.60

T;T;T;T;T;T

Sift4G

Benign

0.49

T;T;T;T;T;T

Polyphen

0.0

B;.;B;B;B;B

Vest4

0.17

MutPred

0.17

.;.;.;Loss of catalytic residue at P485 (P = 0.02);.;Loss of catalytic residue at P485 (P = 0.02);

MVP

0.048

MPC

0.22

ClinPred

0.014

GERP RS

-3.1

Varity_R

0.028

gMVP

0.28

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