rs148926761

Variant names:

• chr22-24495465-A-G
• rs148926761
• NM_016327.3:c.62A>G

Your query was ambiguous. Multiple possible variants found:

• chr22-24495465-A-G
• chr22-24495465-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016327.3(UPB1):​c.62A>G​(p.Asp21Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D21V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: UPB1 NM_016327.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.87
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• beta-ureidopropionase deficiency

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Laboratory for Molecular Medicine

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.265167).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016327.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UPB1	NM_016327.3	MANE Select	c.62A>G	p.Asp21Gly	missense	Exon 1 of 10	NP_057411.1	Q9UBR1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UPB1	ENST00000326010.10	TSL:1 MANE Select	c.62A>G	p.Asp21Gly	missense	Exon 1 of 10	ENSP00000324343.5	Q9UBR1
	UPB1	ENST00000858218.1		c.62A>G	p.Asp21Gly	missense	Exon 1 of 11	ENSP00000528277.1
	UPB1	ENST00000858215.1		c.62A>G	p.Asp21Gly	missense	Exon 1 of 11	ENSP00000528274.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000797 AC: 2 AN: 250878 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.00000274 AC: 4 AN: 1461774 Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3 AN XY: 727192

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53304

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.33	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		5.9
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.30
Sift	Benign	0.056	T
Sift4G	Benign	0.072	T
Polyphen		0.14	B
Vest4		0.25
MutPred		0.18		Gain of MoRF binding (P = 0.0814)
MVP		0.53
MPC		0.18
ClinPred		0.44	T
GERP RS		5.1
PromoterAI		-0.042	Neutral
Varity_R		0.17
gMVP		0.67
Mutation Taster		=63/37	polymorphism

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

Other links and lift over

dbSNP: rs148926761; hg19: chr22-24891433;