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GeneBe

X-38401317-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000531.6(OTC):c.429T>C(p.Tyr143=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000577 in 1,201,001 control chromosomes in the GnomAD database, including 1 homozygotes. There are 179 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 1 hom., 88 hem., cov: 23)
Exomes 𝑓: 0.00032 ( 0 hom. 91 hem. )

Consequence

OTC
NM_000531.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.520
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
Variant X-38401317-T-C is Benign according to our data. Variant chrX-38401317-T-C is described in ClinVar as [Benign]. Clinvar id is 256370.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-38401317-T-C is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=0.52 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00312 (349/111759) while in subpopulation AFR AF= 0.0107 (329/30745). AF 95% confidence interval is 0.00975. There are 1 homozygotes in gnomad4. There are 88 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
BS2
High Hemizygotes in GnomAd at 88 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OTCNM_000531.6 linkuse as main transcriptc.429T>C p.Tyr143= synonymous_variant 5/10 ENST00000039007.5
OTCNM_001407092.1 linkuse as main transcriptc.429T>C p.Tyr143= synonymous_variant 7/12
OTCXM_017029556.2 linkuse as main transcriptc.429T>C p.Tyr143= synonymous_variant 5/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OTCENST00000039007.5 linkuse as main transcriptc.429T>C p.Tyr143= synonymous_variant 5/101 NM_000531.6 P1
OTCENST00000488812.1 linkuse as main transcriptn.466T>C non_coding_transcript_exon_variant 5/65
OTCENST00000643344.1 linkuse as main transcriptc.*179T>C 3_prime_UTR_variant, NMD_transcript_variant 6/11

Frequencies

GnomAD3 genomes
AF:
0.00312
AC:
349
AN:
111708
Hom.:
1
Cov.:
23
AF XY:
0.00260
AC XY:
88
AN XY:
33894
show subpopulations
Gnomad AFR
AF:
0.0107
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00124
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:
0.0000941
Gnomad OTH
AF:
0.00134
GnomAD3 exomes
AF:
0.000976
AC:
178
AN:
182324
Hom.:
0
AF XY:
0.000657
AC XY:
44
AN XY:
66960
show subpopulations
Gnomad AFR exome
AF:
0.0109
Gnomad AMR exome
AF:
0.00121
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000246
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000316
AC:
344
AN:
1089242
Hom.:
0
Cov.:
28
AF XY:
0.000256
AC XY:
91
AN XY:
354994
show subpopulations
Gnomad4 AFR exome
AF:
0.00964
Gnomad4 AMR exome
AF:
0.00111
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:
0.0000144
Gnomad4 OTH exome
AF:
0.000874
GnomAD4 genome
AF:
0.00312
AC:
349
AN:
111759
Hom.:
1
Cov.:
23
AF XY:
0.00259
AC XY:
88
AN XY:
33955
show subpopulations
Gnomad4 AFR
AF:
0.0107
Gnomad4 AMR
AF:
0.00124
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000941
Gnomad4 OTH
AF:
0.00133
Alfa
AF:
0.00273
Hom.:
14
Bravo
AF:
0.00370

ClinVar

Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Benign, criteria provided, single submitterclinical testingGeneDxJun 20, 2016This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Ornithine carbamoyltransferase deficiency Benign:2
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -
Benign, criteria provided, single submitterclinical testingColor Diagnostics, LLC DBA Color HealthMar 27, 2019- -
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitterclinical testingAmbry GeneticsMay 03, 2016This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.54
Cadd
Benign
3.4
Dann
Benign
0.77

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: rs145777402; hg19: chrX-38260570; API