19-4446621-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_025241.3(UBXN6):​c.799C>T​(p.Arg267Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000515 in 1,612,506 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000051 ( 1 hom. )

Consequence

UBXN6
NM_025241.3 missense

Scores

1
11
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.30
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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UBXN6NM_025241.3 linkc.799C>T p.Arg267Cys missense_variant Exon 8 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.799C>T p.Arg267Cys missense_variant Exon 8 of 11 1 NM_025241.3 ENSP00000301281.5 Q9BZV1-1

Frequencies

GnomAD3 genomes
AF:
0.0000591
AC:
9
AN:
152248
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.000105
AC:
26
AN:
248442
AF XY:
0.0000816
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000656
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000448
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.0000507
AC:
74
AN:
1460140
Hom.:
1
Cov.:
32
AF XY:
0.0000509
AC XY:
37
AN XY:
726366
show subpopulations
Gnomad4 AFR exome
AF:
0.00
AC:
0
AN:
33472
Gnomad4 AMR exome
AF:
0.0000895
AC:
4
AN:
44688
Gnomad4 ASJ exome
AF:
0.00
AC:
0
AN:
26106
Gnomad4 EAS exome
AF:
0.000328
AC:
13
AN:
39686
Gnomad4 SAS exome
AF:
0.0000928
AC:
8
AN:
86202
Gnomad4 FIN exome
AF:
0.00
AC:
0
AN:
52114
Gnomad4 NFE exome
AF:
0.0000396
AC:
44
AN:
1111752
Gnomad4 Remaining exome
AF:
0.0000828
AC:
5
AN:
60354
Heterozygous variant carriers
0
6
12
18
24
30
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000591
AC:
9
AN:
152366
Hom.:
0
Cov.:
33
AF XY:
0.0000537
AC XY:
4
AN XY:
74508
show subpopulations
Gnomad4 AFR
AF:
0.0000240
AC:
0.0000240454
AN:
0.0000240454
Gnomad4 AMR
AF:
0.0000653
AC:
0.0000653083
AN:
0.0000653083
Gnomad4 ASJ
AF:
0.00
AC:
0
AN:
0
Gnomad4 EAS
AF:
0.000386
AC:
0.000385802
AN:
0.000385802
Gnomad4 SAS
AF:
0.00
AC:
0
AN:
0
Gnomad4 FIN
AF:
0.00
AC:
0
AN:
0
Gnomad4 NFE
AF:
0.0000735
AC:
0.0000734948
AN:
0.0000734948
Gnomad4 OTH
AF:
0.00
AC:
0
AN:
0
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.000164
Hom.:
0
Bravo
AF:
0.0000604
ExAC
AF:
0.0000824
AC:
10
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 17, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.799C>T (p.R267C) alteration is located in exon 8 (coding exon 8) of the UBXN6 gene. This alteration results from a C to T substitution at nucleotide position 799, causing the arginine (R) at amino acid position 267 to be replaced by a cysteine (C). 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
0.21
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.14
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.25
T;.
Eigen
Uncertain
0.20
Eigen_PC
Benign
0.049
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Uncertain
0.95
D;D
M_CAP
Uncertain
0.12
D
MetaRNN
Uncertain
0.56
D;D
MetaSVM
Benign
-0.92
T
MutationAssessor
Uncertain
2.8
M;.
PrimateAI
Uncertain
0.60
T
PROVEAN
Pathogenic
-5.0
D;D
REVEL
Uncertain
0.30
Sift
Uncertain
0.0060
D;D
Sift4G
Uncertain
0.0090
D;D
Polyphen
1.0
D;D
Vest4
0.74
MVP
0.55
MPC
0.087
ClinPred
0.52
D
GERP RS
1.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.30
gMVP
0.49
Mutation Taster
=44/56
disease causing

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: rs201394926; hg19: chr19-4446618; COSMIC: COSV56671206; COSMIC: COSV56671206; API