22-24495341-C-T

Variant names:

• chr22-24495341-C-T
• rs116629687
• NM_016327.3:c.-63C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_016327.3(UPB1):​c.-63C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000847 in 1,576,962 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0044 (9 hom., cov: 32)
  • Exomes 𝑓: 0.00046 (8 hom.)
• Consequence: UPB1 NM_016327.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.51
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 22-24495341-C-T is Benign according to our data. Variant chr22-24495341-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 340924.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00444 (677/152364) while in subpopulation AFR AF = 0.0154 (641/41582). AF 95% confidence interval is 0.0144. There are 9 homozygotes in GnomAd4. There are 349 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

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.-63C>T		5_prime_UTR	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.-63C>T		5_prime_UTR	Exon 1 of 10	ENSP00000324343.5	Q9UBR1
	UPB1	ENST00000858218.1		c.-63C>T		5_prime_UTR	Exon 1 of 11	ENSP00000528277.1
	UPB1	ENST00000858215.1		c.-63C>T		5_prime_UTR	Exon 1 of 11	ENSP00000528274.1

Frequencies

GnomAD3 genomes AF: 0.00443 AC: 675 AN: 152246 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0154

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00382

GnomAD4 exome AF: 0.000463 AC: 659 AN: 1424598 Hom.: 8 Cov.: 28 AF XY: 0.000369 AC XY: 262 AN XY: 710782

African (AFR) AF: 0.0158 AC: 518 AN: 32852

American (AMR) AF: 0.000649 AC: 29 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25928

East Asian (EAS) AF: 0.00 AC: 0 AN: 39526

South Asian (SAS) AF: 0.0000584 AC: 5 AN: 85660

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46258

Middle Eastern (MID) AF: 0.000575 AC: 3 AN: 5216

European-Non Finnish (NFE) AF: 0.0000452 AC: 49 AN: 1085212

Other (OTH) AF: 0.000928 AC: 55 AN: 59288

GnomAD4 genome AF: 0.00444 AC: 677 AN: 152364 Hom.: 9 Cov.: 32 AF XY: 0.00468 AC XY: 349 AN XY: 74512

African (AFR) AF: 0.0154 AC: 641 AN: 41582

American (AMR) AF: 0.00157 AC: 24 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68034

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.00352 Hom.: 0

Bravo AF: 0.00491

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Deficiency of beta-ureidopropionase (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.8
DANN	Benign	0.93
PhyloP100		1.5
PromoterAI		-0.44	Neutral
Mutation Taster		=300/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs116629687; hg19: chr22-24891309;