Variant rs62622415 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_000531.6(OTC):c.867+35T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0321 in 1,180,579 control chromosomes in the GnomAD database, including 483 homozygotes. There are 11,736 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 29 hom., 738 hem., cov: 22)

Exomes 𝑓: 0.033 ( 454 hom. 10998 hem. )

Consequence

OTC
NM_000531.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.30

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:

ENSG00000250349 (HGNC:):

ENSG00000250349 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.23).

BP6

Variant X-38409060-T-G is Benign according to our data. Variant chrX-38409060-T-G is described in ClinVar as [Benign]. Clinvar id is 256372.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0242 (2706/111645) while in subpopulation NFE AF= 0.0357 (1892/53042). AF 95% confidence interval is 0.0343. There are 29 homozygotes in gnomad4. There are 738 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 29 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
OTC	NM_000531.6 linkuse as main transcript	c.867+35T>G	intron_variant	ENST00000039007.5	NP_000522.3	P00480
OTC	NM_001407092.1 linkuse as main transcript	c.867+35T>G	intron_variant		NP_001394021.1
OTC	XM_017029556.2 linkuse as main transcript	c.867+35T>G	intron_variant		XP_016885045.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
OTC	ENST00000039007.5 linkuse as main transcript	c.867+35T>G	intron_variant	1	NM_000531.6	ENSP00000039007.4	P00480
ENSG00000250349	ENST00000465127.1 linkuse as main transcript	c.172-257061T>G	intron_variant	5		ENSP00000417050.1	B4E171
OTC	ENST00000643344.1 linkuse as main transcript	n.*617+35T>G	intron_variant			ENSP00000496606.1	A0A2R8Y829

Frequencies

GnomAD3 genomes

AF:

0.0243

AC:

2712

AN:

111591

Hom.:

Cov.:

AF XY:

0.0219

AC XY:

739

AN XY:

33769

show subpopulations

Gnomad AFR

AF:

0.00890

Gnomad AMI

AF:

0.0189

Gnomad AMR

AF:

0.0285

Gnomad ASJ

AF:

0.0227

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00267

Gnomad FIN

AF:

0.0164

Gnomad MID

AF:

0.0383

Gnomad NFE

AF:

0.0357

Gnomad OTH

AF:

0.0374

GnomAD3 exomes

AF:

0.0231

AC:

4179

AN:

181276

Hom.:

AF XY:

0.0224

AC XY:

1500

AN XY:

66958

show subpopulations

Gnomad AFR exome

AF:

0.00931

Gnomad AMR exome

AF:

0.0171

Gnomad ASJ exome

AF:

0.0243

Gnomad EAS exome

AF:

0.000145

Gnomad SAS exome

AF:

0.00563

Gnomad FIN exome

AF:

0.0181

Gnomad NFE exome

AF:

0.0360

Gnomad OTH exome

AF:

0.0236

GnomAD4 exome

AF:

0.0330

AC:

35242

AN:

1068934

Hom.:

454

Cov.:

AF XY:

0.0326

AC XY:

10998

AN XY:

337042

show subpopulations

Gnomad4 AFR exome

AF:

0.00912

Gnomad4 AMR exome

AF:

0.0192

Gnomad4 ASJ exome

AF:

0.0211

Gnomad4 EAS exome

AF:

0.0000998

Gnomad4 SAS exome

AF:

0.00636

Gnomad4 FIN exome

AF:

0.0185

Gnomad4 NFE exome

AF:

0.0383

Gnomad4 OTH exome

AF:

0.0309

GnomAD4 genome

AF:

0.0242

AC:

2706

AN:

111645

Hom.:

Cov.:

AF XY:

0.0218

AC XY:

738

AN XY:

33833

show subpopulations

Gnomad4 AFR

AF:

0.00885

Gnomad4 AMR

AF:

0.0285

Gnomad4 ASJ

AF:

0.0227

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00267

Gnomad4 FIN

AF:

0.0164

Gnomad4 NFE

AF:

0.0357

Gnomad4 OTH

AF:

0.0363

Alfa

AF:

0.0280

Hom.:

216

Bravo

AF:

0.0264

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Ornithine carbamoyltransferase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Sep 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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