19-4446537-G-A

Variant summary

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

The NM_025241.3(UBXN6):​c.883C>T​(p.Leu295Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,734 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

UBXN6
NM_025241.3 missense

Scores

1
9
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.32
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.883C>T p.Leu295Phe 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.883C>T p.Leu295Phe missense_variant Exon 8 of 11 1 NM_025241.3 ENSP00000301281.5 Q9BZV1-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1459734
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
726250
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:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 09, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.883C>T (p.L295F) 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 883, causing the leucine (L) at amino acid position 295 to be replaced by a phenylalanine (F). 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
0.24
BayesDel_addAF
Benign
0.011
T
BayesDel_noAF
Benign
-0.22
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.26
T;.
Eigen
Uncertain
0.50
Eigen_PC
Uncertain
0.35
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Uncertain
0.89
D;D
M_CAP
Benign
0.067
D
MetaRNN
Uncertain
0.70
D;D
MetaSVM
Benign
-0.58
T
MutationAssessor
Pathogenic
3.0
M;.
PrimateAI
Benign
0.47
T
PROVEAN
Uncertain
-3.3
D;D
REVEL
Benign
0.25
Sift
Uncertain
0.0050
D;D
Sift4G
Uncertain
0.018
D;D
Polyphen
1.0
D;D
Vest4
0.76
MutPred
0.29
Gain of phosphorylation at T296 (P = 0.2077);.;
MVP
0.76
MPC
0.33
ClinPred
0.98
D
GERP RS
3.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.31
gMVP
0.53

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-4446534; API