Variant 22-24495450-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_016327.3(UPB1):c.47A>C(p.His16Pro) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

UPB1
NM_016327.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.27

Variant links:

Genes affected

UPB1 (HGNC:16297): (beta-ureidopropionase 1) This gene encodes a protein that belongs to the CN hydrolase family. Beta-ureidopropionase catalyzes the last step in the pyrimidine degradation pathway. The pyrimidine bases uracil and thymine are degraded via the consecutive action of dihydropyrimidine dehydrogenase (DHPDH), dihydropyrimidinase (DHP) and beta-ureidopropionase (UP) to beta-alanine and beta-aminoisobutyric acid, respectively. UP deficiencies are associated with N-carbamyl-beta-amino aciduria and may lead to abnormalities in neurological activity. [provided by RefSeq, Jul 2008]

UPB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0059156716).

BP6

Variant 22-24495450-A-C is Benign according to our data. Variant chr22-24495450-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 803648.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UPB1	NM_016327.3 linkuse as main transcript	c.47A>C	p.His16Pro	missense_variant	1/10	ENST00000326010.10	NP_057411.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
UPB1	ENST00000326010.10 linkuse as main transcript	c.47A>C	p.His16Pro	missense_variant	1/10	1	NM_016327.3	ENSP00000324343	P1
UPB1	ENST00000382760.2 linkuse as main transcript	c.47A>C	p.His16Pro	missense_variant	1/4	5		ENSP00000372208
UPB1	ENST00000415388.5 linkuse as main transcript	c.47A>C	p.His16Pro	missense_variant, NMD_transcript_variant	1/9	5		ENSP00000400684

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151996

Hom.:

Cov.:

FAILED QC

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

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00316

AC:

4586

AN:

1450438

Hom.:

Cov.:

AF XY:

0.00344

AC XY:

2483

AN XY:

721256

show subpopulations

Gnomad4 AFR exome

AF:

0.00770

Gnomad4 AMR exome

AF:

0.0254

Gnomad4 ASJ exome

AF:

0.000767

Gnomad4 EAS exome

AF:

0.0184

Gnomad4 SAS exome

AF:

0.00156

Gnomad4 FIN exome

AF:

0.0141

Gnomad4 NFE exome

AF:

0.00137

Gnomad4 OTH exome

AF:

0.00239

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000197

AC:

AN:

152112

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0628

AC:

7583

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Deficiency of beta-ureidopropionase

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Uncertain

0.47

T;.

Eigen

Benign

0.028

Eigen_PC

Benign

0.018

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.80

T;T

MetaRNN

Benign

0.0059

T;T

MetaSVM

Uncertain

0.0039

MutationAssessor

Pathogenic

3.1

M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.40

PROVEAN

Pathogenic

-5.4

D;D

REVEL

Uncertain

0.47

Sift

Uncertain

0.0080

D;D

Sift4G

Uncertain

0.0070

D;D

Polyphen

0.23

B;.

Vest4

0.34

MPC

0.24

ClinPred

0.084

GERP RS

5.1

Varity_R

0.70

gMVP

0.84

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