Variant 20-3115464-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_014948.4(UBOX5):c.1258C>T(p.Pro420Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

UBOX5
NM_014948.4 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.24

Variant links:

Genes affected

UBOX5 (HGNC:17777): (U-box domain containing 5) This gene encodes a U-box domain containing protein. The encoded protein interacts with E2 enzymes and may play a role in the ubiquitination pathway. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

UBOX5 links:

UBOX5-AS1 (HGNC:44111): (UBOX5 antisense RNA 1)

UBOX5-AS1 links:

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=0.07430151).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
UBOX5	NM_014948.4 linkuse as main transcript	c.1258C>T	p.Pro420Ser	missense_variant, splice_region_variant	4/5	ENST00000217173.7	NP_055763.1
UBOX5-AS1	NR_038395.1 linkuse as main transcript	n.1308+3712G>A		intron_variant, non_coding_transcript_variant
UBOX5	NM_001267584.2 linkuse as main transcript	c.1258C>T	p.Pro420Ser	missense_variant, splice_region_variant	4/5		NP_001254513.1
UBOX5	NM_199415.3 linkuse as main transcript	c.1256-5150C>T		intron_variant			NP_955447.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBOX5	ENST00000217173.7 linkuse as main transcript	c.1258C>T	p.Pro420Ser	missense_variant, splice_region_variant	4/5	1	NM_014948.4	ENSP00000217173	P1	O94941-1
UBOX5	ENST00000348031.6 linkuse as main transcript	c.1256-5150C>T		intron_variant		1		ENSP00000311726		O94941-2
UBOX5-AS1	ENST00000446537.5 linkuse as main transcript	n.1306+3712G>A		intron_variant, non_coding_transcript_variant		2
UBOX5-AS1	ENST00000454019.1 linkuse as main transcript	n.191-1025G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248528

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134236

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000547

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:

0.00000137

AC:

AN:

1459752

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726136

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 28, 2023

The c.1258C>T (p.P420S) alteration is located in exon 4 (coding exon 3) of the UBOX5 gene. This alteration results from a C to T substitution at nucleotide position 1258, causing the proline (P) at amino acid position 420 to be replaced by a serine (S). 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

0.077

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.023

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.059

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.73

M_CAP

Benign

0.0071

MetaRNN

Benign

0.074

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.30

PROVEAN

Benign

0.40

REVEL

Benign

0.045

Sift

Benign

0.54

Sift4G

Benign

0.82

Polyphen

0.0030

Vest4

0.24

MutPred

0.19

Gain of catalytic residue at P420 (P = 0.0149);

MVP

0.60

MPC

0.27

ClinPred

0.15

GERP RS

4.0

Varity_R

0.070

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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