Variant 3-132672143-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5

The ENST00000356232.10(UBA5):c.778G>A(p.Val260Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,706 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 Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

UBA5
ENST00000356232.10 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 8.15

Variant links:

Genes affected

UBA5 (HGNC:23230): (ubiquitin like modifier activating enzyme 5) This gene encodes a member of the E1-like ubiquitin-activating enzyme family. This protein activates ubiquitin-fold modifier 1, a ubiquitin-like post-translational modifier protein, via the formation of a high-energy thioester bond. Alternative splicing results in multiple transcript variants. A pseudogene of this gene has been identified on chromosome 1. [provided by RefSeq, Feb 2016]

UBA5 links:

NPHP3-ACAD11 (HGNC:):

NPHP3-ACAD11 links:

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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, 0.826

PP5

Variant 3-132672143-G-A is Pathogenic according to our data. Variant chr3-132672143-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 265752.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-132672143-G-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBA5	NM_024818.6 linkuse as main transcript	c.778G>A	p.Val260Met	missense_variant	8/12	ENST00000356232.10	NP_079094.1
NPHP3-ACAD11	NR_037804.1 linkuse as main transcript	n.3995+9771C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBA5	ENST00000356232.10 linkuse as main transcript	c.778G>A	p.Val260Met	missense_variant	8/12	1	NM_024818.6	ENSP00000348565	P1	Q9GZZ9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

250954

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135630

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

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:

6.84e-7

AC:

AN:

1461706

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727156

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Developmental and epileptic encephalopathy, 44

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 10, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

.;T;.;.;.

Eigen

Uncertain

0.63

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

D;D;D;D;.

M_CAP

Benign

0.024

MetaRNN

Pathogenic

0.83

D;D;D;D;D

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.7

.;M;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-2.2

N;N;N;N;N

REVEL

Uncertain

0.31

Sift

Uncertain

0.019

D;D;D;T;D

Sift4G

Uncertain

0.027

D;D;D;D;D

Polyphen

0.72, 0.83

.;P;.;P;.

Vest4

0.86

MutPred

0.70

.;Loss of catalytic residue at V260 (P = 0.0098);Loss of catalytic residue at V260 (P = 0.0098);Loss of catalytic residue at V260 (P = 0.0098);.;

MVP

0.45

MPC

0.52

ClinPred

0.68

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.52

gMVP

0.93

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.81

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.81

Position offset: -3

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