NM_000531.6:c.299-18C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_000531.6(OTC):c.299-18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000841 in 832,805 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. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000084 ( 0 hom. 0 hem. )

Consequence

OTC
NM_000531.6 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -3.19

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

OTC links:

ENSG00000250349 (HGNC:):

ENSG00000250349 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant X-38381324-C-T is Benign according to our data. Variant chrX-38381324-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 256368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-38381324-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 256368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-38381324-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 256368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-38381324-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 256368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-38381324-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 256368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-38381324-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 256368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-38381324-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 256368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-38381324-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 256368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-38381324-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 256368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-38381324-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 256368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-38381324-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 256368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-38381324-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 256368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-38381324-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 256368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-38381324-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 256368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-38381324-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 256368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
OTC	NM_000531.6 link	c.299-18C>T	intron_variant	Intron 3 of 9	ENST00000039007.5	NP_000522.3	P00480
OTC	NM_001407092.1 link	c.299-18C>T	intron_variant	Intron 5 of 11		NP_001394021.1
OTC	XM_017029556.2 link	c.299-18C>T	intron_variant	Intron 3 of 8		XP_016885045.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTC	ENST00000039007.5 link	c.299-18C>T		intron_variant	Intron 3 of 9	1	NM_000531.6	ENSP00000039007.4		P00480
ENSG00000250349	ENST00000465127.1 link	c.172-284797C>T		intron_variant	Intron 3 of 8	5		ENSP00000417050.1		B4E171

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000634

AC:

AN:

94661

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000145

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000240

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000844

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000841

AC:

AN:

832805

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

259755

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000103

AC:

AN:

19340

American (AMR)

AF:

0.0000384

AC:

AN:

26019

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15163

East Asian (EAS)

AF:

0.00

AC:

AN:

23104

South Asian (SAS)

AF:

0.00

AC:

AN:

39213

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33916

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3440

European-Non Finnish (NFE)

AF:

0.00000471

AC:

AN:

637558

Other (OTH)

AF:

0.0000285

AC:

AN:

35052

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.268

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Ornithine carbamoyltransferase deficiency

Benign:1

Jan 17, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.094

(source)

DANN

Benign

0.20

PhyloP100

-3.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over