dbSNP rs748372333: UBOX5:p.Met522Thr (chr20-3110167-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_014948.4(UBOX5):c.1565T>C(p.Met522Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

UBOX5
NM_014948.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.52

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:

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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=0.09078175).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBOX5	NM_014948.4 link	c.1565T>C	p.Met522Thr	missense_variant	Exon 5 of 5	ENST00000217173.7	NP_055763.1	O94941-1
UBOX5	NM_199415.3 link	c.1403T>C	p.Met468Thr	missense_variant	Exon 4 of 4		NP_955447.1	O94941-2
UBOX5	NM_001267584.2 link	c.*21T>C		3_prime_UTR_variant	Exon 5 of 5		NP_001254513.1
UBOX5-AS1	NR_038395.1 link	n.938-111A>G		intron_variant	Intron 2 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
UBOX5	ENST00000217173.7 link	c.1565T>C	p.Met522Thr	missense_variant	Exon 5 of 5	1	NM_014948.4	ENSP00000217173.2	O94941-1
UBOX5	ENST00000348031.6 link	c.1403T>C	p.Met468Thr	missense_variant	Exon 4 of 4	1		ENSP00000311726.3	O94941-2
UBOX5-AS1	ENST00000446537.5 link	n.936-111A>G		intron_variant	Intron 2 of 6	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251280

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135882

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.067

T;.

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.50

T;T

M_CAP

Benign

0.033

MetaRNN

Benign

0.091

T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.5

L;.

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.91

N;N

REVEL

Benign

0.064

Sift

Benign

0.080

T;T

Sift4G

Uncertain

0.010

D;D

Polyphen

0.0

B;.

Vest4

0.15

MutPred

0.35

Gain of glycosylation at M522 (P = 0.0531);.;

MVP

0.72

MPC

0.31

ClinPred

0.32

GERP RS

2.8

Varity_R

0.12

gMVP

0.34

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over