GeneBe

X-38401332-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000531.6(OTC):​c.444G>A​(p.Leu148Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000185 in 1,082,045 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 23)
Exomes 𝑓: 0.0000018 ( 0 hom. 0 hem. )

Consequence

OTC
NM_000531.6 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.83

Publications

0 publications found
Variant links:
Genes affected
OTC (HGNC:8512): (ornithine transcarbamylase) This nuclear gene encodes a mitochondrial matrix enzyme. The encoded protein is involved in the urea cycle which functions to detoxify ammonia into urea for excretion. Mutations in this enzyme lead to ornithine transcarbamylase deficiency, which causes hyperammonemia. [provided by RefSeq, May 2022]
OTC Gene-Disease associations (from GenCC):
  • ornithine carbamoyltransferase deficiency
    Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Laboratory for Molecular Medicine, Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.4).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OTCNM_000531.6 linkc.444G>A p.Leu148Leu synonymous_variant Exon 5 of 10 ENST00000039007.5 NP_000522.3 P00480
OTCNM_001407092.1 linkc.444G>A p.Leu148Leu synonymous_variant Exon 7 of 12 NP_001394021.1
OTCXM_017029556.2 linkc.444G>A p.Leu148Leu synonymous_variant Exon 5 of 9 XP_016885045.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OTCENST00000039007.5 linkc.444G>A p.Leu148Leu synonymous_variant Exon 5 of 10 1 NM_000531.6 ENSP00000039007.4 P00480
ENSG00000250349ENST00000465127.1 linkc.172-264789G>A intron_variant Intron 3 of 8 5 ENSP00000417050.1 B4E171

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
AF:
0.00000185
AC:
2
AN:
1082045
Hom.:
0
Cov.:
28
AF XY:
0.00
AC XY:
0
AN XY:
348177
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
26107
American (AMR)
AF:
0.00
AC:
0
AN:
35180
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
19282
East Asian (EAS)
AF:
0.0000332
AC:
1
AN:
30101
South Asian (SAS)
AF:
0.00
AC:
0
AN:
53672
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
40479
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4088
European-Non Finnish (NFE)
AF:
0.00000121
AC:
1
AN:
827540
Other (OTH)
AF:
0.00
AC:
0
AN:
45596
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.40
CADD
Benign
8.7
DANN
Benign
0.76
PhyloP100
3.8

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

Other links and lift over

dbSNP: rs66741318; hg19: chrX-38260585; API