Variant 22-24495444-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016327.3(UPB1):c.41A>G(p.Glu14Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000744 in 1,613,632 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

UPB1
NM_016327.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.87

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UPB1	NM_016327.3 linkuse as main transcript	c.41A>G	p.Glu14Gly	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.41A>G	p.Glu14Gly	missense_variant	1/10	1	NM_016327.3	ENSP00000324343	P1
UPB1	ENST00000382760.2 linkuse as main transcript	c.41A>G	p.Glu14Gly	missense_variant	1/4	5		ENSP00000372208
UPB1	ENST00000415388.5 linkuse as main transcript	c.41A>G	p.Glu14Gly	missense_variant, NMD_transcript_variant	1/9	5		ENSP00000400684

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152192

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

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461440

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727058

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000989

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74356

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

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 24, 2024

The c.41A>G (p.E14G) alteration is located in exon 1 (coding exon 1) of the UPB1 gene. This alteration results from a A to G substitution at nucleotide position 41, causing the glutamic acid (E) at amino acid position 14 to be replaced by a glycine (G). 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

0.091

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.010

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.48

T;.

Eigen

Benign

-0.023

Eigen_PC

Benign

0.061

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.85

T;T

M_CAP

Benign

0.050

MetaRNN

Uncertain

0.49

T;T

MetaSVM

Benign

-0.35

MutationAssessor

Uncertain

2.2

M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.9

D;D

REVEL

Uncertain

0.42

Sift

Benign

0.030

D;D

Sift4G

Uncertain

0.039

D;T

Polyphen

0.019

B;.

Vest4

0.54

MutPred

0.26

Loss of stability (P = 0.0351);Loss of stability (P = 0.0351);

MVP

0.84

MPC

0.14

ClinPred

0.91

GERP RS

5.1

Varity_R

0.37

gMVP

0.59

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