19-4445562-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_025241.3(UBXN6):​c.1262C>T​(p.Ala421Val) variant causes a missense change. The variant allele was found at a frequency of 0.000346 in 1,613,820 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 0.00032 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00035 ( 0 hom. )

Consequence

UBXN6
NM_025241.3 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.82
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07768616).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UBXN6NM_025241.3 linkc.1262C>T p.Ala421Val 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.1262C>T p.Ala421Val missense_variant Exon 11 of 11 1 NM_025241.3 ENSP00000301281.5 Q9BZV1-1

Frequencies

GnomAD3 genomes
AF:
0.000322
AC:
49
AN:
152230
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000941
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000617
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000329
AC:
82
AN:
248956
Hom.:
0
AF XY:
0.000341
AC XY:
46
AN XY:
134800
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000174
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.000185
Gnomad NFE exome
AF:
0.000611
Gnomad OTH exome
AF:
0.000327
GnomAD4 exome
AF:
0.000348
AC:
509
AN:
1461472
Hom.:
0
Cov.:
31
AF XY:
0.000349
AC XY:
254
AN XY:
727062
show subpopulations
Gnomad4 AFR exome
AF:
0.000149
Gnomad4 AMR exome
AF:
0.000201
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.000226
Gnomad4 NFE exome
AF:
0.000418
Gnomad4 OTH exome
AF:
0.000265
GnomAD4 genome
AF:
0.000322
AC:
49
AN:
152348
Hom.:
0
Cov.:
33
AF XY:
0.000255
AC XY:
19
AN XY:
74504
show subpopulations
Gnomad4 AFR
AF:
0.0000962
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000941
Gnomad4 NFE
AF:
0.000617
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000403
Hom.:
0
Bravo
AF:
0.000249
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000581
AC:
5
ExAC
AF:
0.000288
AC:
35
EpiCase
AF:
0.000164
EpiControl
AF:
0.000296

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 29, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1262C>T (p.A421V) alteration is located in exon 11 (coding exon 11) of the UBXN6 gene. This alteration results from a C to T substitution at nucleotide position 1262, causing the alanine (A) at amino acid position 421 to be replaced by a valine (V). 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
-0.27
T
BayesDel_noAF
Benign
-0.22
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.034
T;.
Eigen
Benign
0.17
Eigen_PC
Benign
0.17
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.86
D;D
M_CAP
Benign
0.024
T
MetaRNN
Benign
0.078
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.5
M;.
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-2.0
N;N
REVEL
Benign
0.20
Sift
Uncertain
0.0090
D;D
Sift4G
Uncertain
0.014
D;D
Polyphen
1.0
D;P
Vest4
0.25
MVP
0.71
MPC
0.25
ClinPred
0.11
T
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.088
gMVP
0.51

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: rs77077573; hg19: chr19-4445559; COSMIC: COSV56673343; COSMIC: COSV56673343; API