1-20191037-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152376.5(UBXN10):​c.476G>A​(p.Ser159Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000062 in 1,613,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

UBXN10
NM_152376.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.103
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.01059404).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UBXN10NM_152376.5 linkc.476G>A p.Ser159Asn missense_variant Exon 2 of 2 ENST00000375099.4 NP_689589.1 Q96LJ8
UBXN10XM_005245742.5 linkc.476G>A p.Ser159Asn missense_variant Exon 2 of 2 XP_005245799.1 Q96LJ8
UBXN10XM_011540699.4 linkc.476G>A p.Ser159Asn 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.476G>A p.Ser159Asn missense_variant Exon 2 of 2 1 NM_152376.5 ENSP00000364240.3 Q96LJ8

Frequencies

GnomAD3 genomes
AF:
0.000276
AC:
42
AN:
152116
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00101
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000915
AC:
23
AN:
251252
Hom.:
1
AF XY:
0.0000515
AC XY:
7
AN XY:
135850
show subpopulations
Gnomad AFR exome
AF:
0.00118
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:
0.000163
GnomAD4 exome
AF:
0.0000397
AC:
58
AN:
1461760
Hom.:
0
Cov.:
31
AF XY:
0.0000275
AC XY:
20
AN XY:
727174
show subpopulations
Gnomad4 AFR exome
AF:
0.00143
Gnomad4 AMR exome
AF:
0.0000447
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:
0.000116
GnomAD4 genome
AF:
0.000276
AC:
42
AN:
152234
Hom.:
0
Cov.:
32
AF XY:
0.000228
AC XY:
17
AN XY:
74438
show subpopulations
Gnomad4 AFR
AF:
0.00101
Gnomad4 AMR
AF:
0.00
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
Alfa
AF:
0.000364
Hom.:
0
Bravo
AF:
0.000382
ESP6500AA
AF:
0.00113
AC:
5
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000988
AC:
12

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 06, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.476G>A (p.S159N) alteration is located in exon 2 (coding exon 1) of the UBXN10 gene. This alteration results from a G to A substitution at nucleotide position 476, causing the serine (S) at amino acid position 159 to be replaced by an asparagine (N). 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
0.090
BayesDel_addAF
Benign
-0.66
T
BayesDel_noAF
Benign
-0.78
CADD
Benign
5.0
DANN
Benign
0.82
DEOGEN2
Benign
0.034
T
Eigen
Benign
-0.98
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.031
N
LIST_S2
Benign
0.27
T
M_CAP
Benign
0.0020
T
MetaRNN
Benign
0.011
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.2
L
PrimateAI
Benign
0.21
T
PROVEAN
Benign
-0.41
N
REVEL
Benign
0.027
Sift
Benign
0.19
T
Sift4G
Benign
0.45
T
Polyphen
0.0
B
Vest4
0.027
MVP
0.014
MPC
0.12
ClinPred
0.0059
T
GERP RS
2.8
Varity_R
0.051
gMVP
0.18

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: rs138479642; hg19: chr1-20517530; API