NM_024818.6:c.20G>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_024818.6(UBA5):c.20G>A(p.Arg7His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000196 in 1,549,556 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R7C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 1 hom. )

Consequence

UBA5
NM_024818.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.29

Publications

0 publications found

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:48351): (NPHP3-ACAD11 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring NPHP3 (nephronophthisis 3, adolescent) and ACAD11 (acyl-CoA dehydrogenase family, member 11) genes on chromosome 3. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

NPHP3-ACAD11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0152903795).

BP6

Variant 3-132660557-G-A is Benign according to our data. Variant chr3-132660557-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1631850.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024818.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBA5	NM_024818.6	MANE Select	c.20G>A	p.Arg7His	missense	Exon 1 of 12	NP_079094.1	Q9GZZ9-1
UBA5	NM_001320210.2		c.-499G>A		5_prime_UTR	Exon 1 of 12	NP_001307139.1	Q9GZZ9-2
UBA5	NM_001321238.2		c.-465G>A		5_prime_UTR	Exon 1 of 10	NP_001308167.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBA5	ENST00000356232.10	TSL:1 MANE Select	c.20G>A	p.Arg7His	missense	Exon 1 of 12	ENSP00000348565.4	Q9GZZ9-1
UBA5	ENST00000494238.6	TSL:1	c.-499G>A		5_prime_UTR	Exon 1 of 12	ENSP00000418807.2	Q9GZZ9-2
NPHP3-ACAD11	ENST00000632629.1	TSL:2	c.636-15661C>T		intron	N/A	ENSP00000488520.1	A0A0J9YXS1

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000324

AC:

AN:

154558

AF XY:

0.000282

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000809

Gnomad ASJ exome

AF:

0.00330

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000270

Gnomad OTH exome

AF:

0.000912

GnomAD4 exome

AF:

0.000194

AC:

271

AN:

1397360

Hom.:

Cov.:

AF XY:

0.000197

AC XY:

136

AN XY:

689270

show subpopulations

African (AFR)

AF:

0.0000317

AC:

AN:

31586

American (AMR)

AF:

0.0000560

AC:

AN:

35716

Ashkenazi Jewish (ASJ)

AF:

0.00318

AC:

AN:

25166

East Asian (EAS)

AF:

0.00

AC:

AN:

35796

South Asian (SAS)

AF:

0.00

AC:

AN:

79178

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48420

Middle Eastern (MID)

AF:

0.000449

AC:

AN:

4452

European-Non Finnish (NFE)

AF:

0.000143

AC:

154

AN:

1079166

Other (OTH)

AF:

0.000553

AC:

AN:

57880

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000210

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41448

American (AMR)

AF:

0.0000654

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000221

AC:

AN:

68026

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000491

Hom.:

Bravo

AF:

0.000208

ExAC

AF:

0.000148

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.098

Eigen

Benign

0.055

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.25

LIST_S2

Uncertain

0.86

M_CAP

Pathogenic

0.58

MetaRNN

Benign

0.015

MetaSVM

Benign

-0.42

MutationAssessor

Benign

1.8

PhyloP100

1.3

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.43

REVEL

Uncertain

0.37

Sift

Benign

0.036

Sift4G

Uncertain

0.044

Polyphen

0.71

Vest4

0.23

MVP

0.41

MPC

0.39

ClinPred

0.14

GERP RS

4.0

PromoterAI

-0.21

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.081

gMVP

0.26

Mutation Taster

=79/21

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over