Genetic Variant UBXN10:p.Gly44Arg (chr1-20190691-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_152376.5(UBXN10):c.130G>A(p.Gly44Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,612,626 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

UBXN10
NM_152376.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.17

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]

UBXN10 links:

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
UBXN10	NM_152376.5 link	c.130G>A	p.Gly44Arg	missense_variant	Exon 2 of 2	ENST00000375099.4	NP_689589.1	Q96LJ8
UBXN10	XM_005245742.5 link	c.130G>A	p.Gly44Arg	missense_variant	Exon 2 of 2		XP_005245799.1	Q96LJ8
UBXN10	XM_011540699.4 link	c.130G>A	p.Gly44Arg	missense_variant	Exon 2 of 2		XP_011539001.1	Q96LJ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBXN10	ENST00000375099.4 link	c.130G>A	p.Gly44Arg	missense_variant	Exon 2 of 2	1	NM_152376.5	ENSP00000364240.3		Q96LJ8

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

151964

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

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:

0.00000400

AC:

AN:

249944

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135232

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460662

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726612

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000329

AC:

AN:

151964

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.000121

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

Bravo

AF:

0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.130G>A (p.G44R) 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 130, causing the glycine (G) at amino acid position 44 to be replaced by an arginine (R). 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

0.95

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

0.080

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.48

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.71

M_CAP

Benign

0.028

MetaRNN

Uncertain

0.55

MetaSVM

Uncertain

-0.13

MutationAssessor

Uncertain

2.3

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-6.6

REVEL

Uncertain

0.52

Sift

Uncertain

0.021

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.42

MutPred

0.56

Gain of solvent accessibility (P = 0.0037);

MVP

0.13

MPC

0.66

ClinPred

0.99

GERP RS

5.2

Varity_R

0.37

gMVP

0.49

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over