X-38352649-G-T

Position:

chrX-38352649-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000531.6(OTC):c.-48G>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 0.00083 in 1,013,723 control chromosomes in the GnomAD database, including 2 homozygotes. There are 278 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00086 ( 0 hom., 45 hem., cov: 23)

Exomes 𝑓: 0.00083 ( 2 hom. 233 hem. )

Consequence

OTC
NM_000531.6 5_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.77

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant X-38352649-G-T is Benign according to our data. Variant chrX-38352649-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 368256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.000826 (745/901940) while in subpopulation EAS AF= 0.00346 (101/29200). AF 95% confidence interval is 0.00291. There are 2 homozygotes in gnomad4_exome. There are 233 alleles in male gnomad4_exome subpopulation. Median coverage is 15. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 45 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
OTC	NM_000531.6 linkuse as main transcript	c.-48G>T	5_prime_UTR_variant	1/10	ENST00000039007.5
OTC	NM_001407092.1 linkuse as main transcript	c.-48G>T	5_prime_UTR_variant	3/12
OTC	XM_017029556.2 linkuse as main transcript	c.-48G>T	5_prime_UTR_variant	1/9

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
OTC	ENST00000039007.5 linkuse as main transcript	c.-48G>T	5_prime_UTR_variant	1/10	1	NM_000531.6	P1
OTC	ENST00000488812.1 linkuse as main transcript	n.45G>T	non_coding_transcript_exon_variant	1/6	5
OTC	ENST00000643344.1 linkuse as main transcript	c.-48G>T	5_prime_UTR_variant, NMD_transcript_variant	1/11

Frequencies

GnomAD3 genomes

AF:

0.000868

AC:

AN:

111727

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

AN XY:

33891

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000560

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0123

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000395

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00143

AC:

256

AN:

179277

Hom.:

AF XY:

0.00120

AC XY:

AN XY:

64121

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000662

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0127

Gnomad NFE exome

AF:

0.000415

Gnomad OTH exome

AF:

0.00383

GnomAD4 exome

AF:

0.000826

AC:

745

AN:

901940

Hom.:

Cov.:

AF XY:

0.000897

AC XY:

233

AN XY:

259832

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00346

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0133

Gnomad4 NFE exome

AF:

0.000108

Gnomad4 OTH exome

AF:

0.00101

GnomAD4 genome

AF:

0.000859

AC:

AN:

111783

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

AN XY:

33957

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000281

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0123

Gnomad4 NFE

AF:

0.000395

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000727

Hom.:

Bravo

AF:

0.0000793

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Ornithine carbamoyltransferase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 16, 2022

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.78

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over