1-20191343-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_152376.5(UBXN10):​c.782G>T​(p.Cys261Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,614,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

UBXN10
NM_152376.5 missense

Scores

10
6
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.79
Variant links:
Genes affected
UBXN10 (HGNC:26354): (UBX domain protein 10) Involved in cilium assembly. Located in cilium. Colocalizes with intraciliary transport particle B. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.883

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UBXN10NM_152376.5 linkc.782G>T p.Cys261Phe missense_variant Exon 2 of 2 ENST00000375099.4 NP_689589.1 Q96LJ8
UBXN10XM_005245742.5 linkc.782G>T p.Cys261Phe missense_variant Exon 2 of 2 XP_005245799.1 Q96LJ8
UBXN10XM_011540699.4 linkc.782G>T p.Cys261Phe missense_variant Exon 2 of 2 XP_011539001.1 Q96LJ8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UBXN10ENST00000375099.4 linkc.782G>T p.Cys261Phe missense_variant Exon 2 of 2 1 NM_152376.5 ENSP00000364240.3 Q96LJ8

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152236
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251378
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135890
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000867
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461874
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000112
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152236
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 01, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.782G>T (p.C261F) alteration is located in exon 2 (coding exon 1) of the UBXN10 gene. This alteration results from a G to T substitution at nucleotide position 782, causing the cysteine (C) at amino acid position 261 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
Pathogenic
0.86
BayesDel_addAF
Pathogenic
0.30
D
BayesDel_noAF
Pathogenic
0.38
CADD
Pathogenic
30
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.47
T
Eigen
Pathogenic
0.91
Eigen_PC
Pathogenic
0.90
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.72
T
M_CAP
Benign
0.023
T
MetaRNN
Pathogenic
0.88
D
MetaSVM
Uncertain
-0.13
T
MutationAssessor
Uncertain
2.5
M
PrimateAI
Uncertain
0.65
T
PROVEAN
Pathogenic
-8.8
D
REVEL
Pathogenic
0.75
Sift
Uncertain
0.011
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.83
MutPred
0.70
Gain of MoRF binding (P = 0.0694);
MVP
0.24
MPC
0.76
ClinPred
0.99
D
GERP RS
6.0
Varity_R
0.85
gMVP
0.64

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: rs1481977160; hg19: chr1-20517836; API