chr22-24495450-A-C

Variant summary

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

The NM_016327.3(UPB1):ā€‹c.47A>Cā€‹(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 (ā˜…).

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 32)
Exomes š‘“: 0.0032 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

UPB1
NM_016327.3 missense

Scores

2
9
7

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]

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
UPB1NM_016327.3 linkuse as main transcriptc.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 UniProt
UPB1ENST00000326010.10 linkuse as main transcriptc.47A>C p.His16Pro missense_variant 1/101 NM_016327.3 ENSP00000324343 P1
UPB1ENST00000382760.2 linkuse as main transcriptc.47A>C p.His16Pro missense_variant 1/45 ENSP00000372208
UPB1ENST00000415388.5 linkuse as main transcriptc.47A>C p.His16Pro missense_variant, NMD_transcript_variant 1/95 ENSP00000400684

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
1
AN:
151996
Hom.:
0
Cov.:
32
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.:
0
Cov.:
33
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:
3
AN:
152112
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
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 submitterclinical testingMendelicsMay 28, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.36
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Uncertain
-0.080
CADD
Uncertain
24
DANN
Benign
0.96
DEOGEN2
Uncertain
0.47
T;.
Eigen
Benign
0.028
Eigen_PC
Benign
0.018
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.80
T;T
MetaRNN
Benign
0.0059
T;T
MetaSVM
Uncertain
0.0039
D
MutationAssessor
Pathogenic
3.1
M;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Benign
0.40
T
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
T
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.

Other links and lift over

dbSNP: rs199934207; hg19: chr22-24891418; COSMIC: COSV58115145; COSMIC: COSV58115145; API