Variant 19-4445584-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_025241.3(UBXN6):c.1240G>A(p.Val414Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 1,613,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

UBXN6
NM_025241.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.78

Variant links:

Genes affected

UBXN6 (HGNC:14928): (UBX domain protein 6) Involved in ERAD pathway; endosome to lysosome transport via multivesicular body sorting pathway; and macroautophagy. Located in bounding membrane of organelle and cytosol. Is extrinsic component of membrane. Part of endosome and protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

UBXN6 links:

CHAF1A (HGNC:):

CHAF1A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.39970952).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBXN6	NM_025241.3 linkuse as main transcript	c.1240G>A	p.Val414Met	missense_variant	11/11	ENST00000301281.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBXN6	ENST00000301281.11 linkuse as main transcript	c.1240G>A	p.Val414Met	missense_variant	11/11	1	NM_025241.3	P1	Q9BZV1-1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.000220

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000157

AC:

AN:

248814

Hom.:

AF XY:

0.000193

AC XY:

AN XY:

134740

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:

0.0000925

Gnomad NFE exome

AF:

0.000324

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000127

AC:

185

AN:

1461402

Hom.:

Cov.:

AF XY:

0.000111

AC XY:

AN XY:

727032

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:

0.000283

Gnomad4 NFE exome

AF:

0.000143

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.000105

AC:

AN:

152350

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.000220

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000158

Hom.:

Bravo

AF:

0.0000793

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000264

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000237

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

Mar 29, 2022

The c.1240G>A (p.V414M) alteration is located in exon 11 (coding exon 11) of the UBXN6 gene. This alteration results from a G to A substitution at nucleotide position 1240, causing the valine (V) at amino acid position 414 to be replaced by a methionine (M). 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

0.30

BayesDel_addAF

Benign

-0.058

BayesDel_noAF

Uncertain

-0.020

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.077

T;.

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.026

MetaRNN

Benign

0.40

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.6

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.21

Sift

Uncertain

0.0060

D;D

Sift4G

Uncertain

0.020

D;D

Polyphen

1.0

D;D

Vest4

0.34

MVP

0.86

MPC

0.31

ClinPred

0.18

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.21

gMVP

0.60

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