19-4445530-C-T

Variant summary

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

The NM_025241.3(UBXN6):​c.1294G>A​(p.Glu432Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000428 in 1,613,818 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

UBXN6
NM_025241.3 missense

Scores

1
11
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.33
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]
CHAF1A (HGNC:1910): (chromatin assembly factor 1 subunit A) Chromatin assembly factor I (CAF1) is a nuclear complex consisting of p50, p60 (CHAF1B; MIM 601245), and p150 (CHAF1A) subunits that assembles histone octamers onto replicating DNA in vitro (Kaufman et al., 1995 [PubMed 7600578]).[supplied by OMIM, Mar 2008]

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 rank MANE Protein UniProt
UBXN6NM_025241.3 linkc.1294G>A p.Glu432Lys missense_variant Exon 11 of 11 ENST00000301281.11 NP_079517.1 Q9BZV1-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UBXN6ENST00000301281.11 linkc.1294G>A p.Glu432Lys missense_variant Exon 11 of 11 1 NM_025241.3 ENSP00000301281.5 Q9BZV1-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152220
Hom.:
0
Cov.:
33
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:
0.000193
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:
0.0000361
AC:
9
AN:
249106
Hom.:
0
AF XY:
0.0000371
AC XY:
5
AN XY:
134844
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000202
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:
0.00000897
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000452
AC:
66
AN:
1461598
Hom.:
0
Cov.:
31
AF XY:
0.0000454
AC XY:
33
AN XY:
727120
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000179
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000453
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000333
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152220
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74364
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.0000412
AC:
5
EpiCase
AF:
0.000327
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 20, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1294G>A (p.E432K) 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 1294, causing the glutamic acid (E) at amino acid position 432 to be replaced by a lysine (K). 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
0.16
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.21
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.23
T;.
Eigen
Uncertain
0.48
Eigen_PC
Uncertain
0.47
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.94
D;D
M_CAP
Benign
0.058
D
MetaRNN
Uncertain
0.47
T;T
MetaSVM
Benign
-0.89
T
MutationAssessor
Uncertain
2.6
M;.
PrimateAI
Uncertain
0.55
T
PROVEAN
Uncertain
-3.2
D;D
REVEL
Uncertain
0.31
Sift
Uncertain
0.0080
D;D
Sift4G
Uncertain
0.016
D;D
Polyphen
1.0
D;D
Vest4
0.47
MutPred
0.58
Gain of ubiquitination at E432 (P = 0.0146);.;
MVP
0.83
MPC
0.27
ClinPred
0.84
D
GERP RS
5.7
Varity_R
0.33
gMVP
0.79

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.

Other links and lift over

dbSNP: rs138129036; hg19: chr19-4445527; API