Variant rs957415 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000531.6(OTC):c.663+50A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0042 in 1,164,513 control chromosomes in the GnomAD database, including 9 homozygotes. There are 1,613 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0030 ( 1 hom., 97 hem., cov: 23)

Exomes 𝑓: 0.0043 ( 8 hom. 1516 hem. )

Consequence

OTC
NM_000531.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.209

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant X-38403790-A-G is Benign according to our data. Variant chrX-38403790-A-G is described in ClinVar as [Benign]. Clinvar id is 256371.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 = 0.00297 (332/111823) while in subpopulation NFE AF= 0.00485 (258/53158). AF 95% confidence interval is 0.00437. There are 1 homozygotes in gnomad4. There are 97 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 97 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
OTC	NM_000531.6 linkuse as main transcript	c.663+50A>G	intron_variant	ENST00000039007.5	NP_000522.3
OTC	NM_001407092.1 linkuse as main transcript	c.663+50A>G	intron_variant		NP_001394021.1
OTC	XM_017029556.2 linkuse as main transcript	c.663+50A>G	intron_variant		XP_016885045.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OTC	ENST00000039007.5 linkuse as main transcript	c.663+50A>G		intron_variant		1	NM_000531.6	ENSP00000039007	P1
OTC	ENST00000643344.1 linkuse as main transcript	c.*413+50A>G		intron_variant, NMD_transcript_variant				ENSP00000496606

Frequencies

GnomAD3 genomes

AF:

0.00297

AC:

332

AN:

111770

Hom.:

Cov.:

AF XY:

0.00286

AC XY:

AN XY:

33956

show subpopulations

Gnomad AFR

AF:

0.000650

Gnomad AMI

AF:

0.00438

Gnomad AMR

AF:

0.00247

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00419

Gnomad FIN

AF:

0.000657

Gnomad MID

AF:

0.0168

Gnomad NFE

AF:

0.00485

Gnomad OTH

AF:

0.00403

GnomAD3 exomes

AF:

0.00275

AC:

498

AN:

180767

Hom.:

AF XY:

0.00326

AC XY:

215

AN XY:

65993

show subpopulations

Gnomad AFR exome

AF:

0.000613

Gnomad AMR exome

AF:

0.00102

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00380

Gnomad FIN exome

AF:

0.000906

Gnomad NFE exome

AF:

0.00452

Gnomad OTH exome

AF:

0.00290

GnomAD4 exome

AF:

0.00433

AC:

4558

AN:

1052690

Hom.:

Cov.:

AF XY:

0.00470

AC XY:

1516

AN XY:

322506

show subpopulations

Gnomad4 AFR exome

AF:

0.000625

Gnomad4 AMR exome

AF:

0.00120

Gnomad4 ASJ exome

AF:

0.000105

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00392

Gnomad4 FIN exome

AF:

0.000999

Gnomad4 NFE exome

AF:

0.00507

Gnomad4 OTH exome

AF:

0.00370

GnomAD4 genome

AF:

0.00297

AC:

332

AN:

111823

Hom.:

Cov.:

AF XY:

0.00285

AC XY:

AN XY:

34019

show subpopulations

Gnomad4 AFR

AF:

0.000649

Gnomad4 AMR

AF:

0.00247

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00420

Gnomad4 FIN

AF:

0.000657

Gnomad4 NFE

AF:

0.00485

Gnomad4 OTH

AF:

0.00398

Alfa

AF:

0.00386

Hom.:

Bravo

AF:

0.00267

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.5

DANN

Benign

0.61

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.

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