dbSNP rs398122026: OTC:c.299-34dupT (chrX-38381302-G-GT) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000531.6(OTC):c.299-34dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1383 hom., 4501 hem., cov: 19)

Exomes 𝑓: 0.19 ( 14044 hom. 48998 hem. )

Consequence

OTC
NM_000531.6 intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: -0.498

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 -16 ACMG points.

BP6

Variant X-38381302-G-GT is Benign according to our data. Variant chrX-38381302-G-GT is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 256369.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
OTC	NM_000531.6 link	c.299-34dupT	intron_variant	Intron 3 of 9	ENST00000039007.5	NP_000522.3	P00480
OTC	NM_001407092.1 link	c.299-34dupT	intron_variant	Intron 5 of 11		NP_001394021.1
OTC	XM_017029556.2 link	c.299-34dupT	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.299-40_299-39insT		intron_variant	Intron 3 of 9	1	NM_000531.6	ENSP00000039007.4		P00480
ENSG00000250349	ENST00000465127.1 link	c.172-284819_172-284818insT		intron_variant	Intron 3 of 8	5		ENSP00000417050.1		B4E171

Frequencies

GnomAD3 genomes

AF:

0.153

AC:

16831

AN:

110215

Hom.:

1384

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0364

Gnomad AMI

AF:

0.386

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.268

Gnomad EAS

AF:

0.000563

Gnomad SAS

AF:

0.0330

Gnomad FIN

AF:

0.143

Gnomad MID

AF:

0.271

Gnomad NFE

AF:

0.232

Gnomad OTH

AF:

0.175

GnomAD2 exomes

AF:

0.152

AC:

22773

AN:

149406

AF XY:

0.154

show subpopulations

Gnomad AFR exome

AF:

0.0329

Gnomad AMR exome

AF:

0.0905

Gnomad ASJ exome

AF:

0.278

Gnomad EAS exome

AF:

0.000346

Gnomad FIN exome

AF:

0.165

Gnomad NFE exome

AF:

0.225

Gnomad OTH exome

AF:

0.200

GnomAD4 exome

AF:

0.193

AC:

175662

AN:

908627

Hom.:

14044

Cov.:

AF XY:

0.190

AC XY:

48998

AN XY:

257999

show subpopulations

African (AFR)

AF:

0.0369

AC:

814

AN:

22083

American (AMR)

AF:

0.0982

AC:

3012

AN:

30670

Ashkenazi Jewish (ASJ)

AF:

0.277

AC:

4886

AN:

17617

East Asian (EAS)

AF:

0.000481

AC:

AN:

29098

South Asian (SAS)

AF:

0.0513

AC:

2366

AN:

46135

European-Finnish (FIN)

AF:

0.170

AC:

6724

AN:

39604

Middle Eastern (MID)

AF:

0.253

AC:

935

AN:

3693

European-Non Finnish (NFE)

AF:

0.220

AC:

149552

AN:

680202

Other (OTH)

AF:

0.186

AC:

7359

AN:

39525

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

4574

9149

13723

18298

22872

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4680

9360

14040

18720

23400

<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

AF:

0.153

AC:

16821

AN:

110264

Hom.:

1383

Cov.:

AF XY:

0.138

AC XY:

4501

AN XY:

32674

show subpopulations

African (AFR)

AF:

0.0363

AC:

1110

AN:

30542

American (AMR)

AF:

0.133

AC:

1371

AN:

10318

Ashkenazi Jewish (ASJ)

AF:

0.268

AC:

697

AN:

2603

East Asian (EAS)

AF:

0.000565

AC:

AN:

3538

South Asian (SAS)

AF:

0.0324

AC:

AN:

2654

European-Finnish (FIN)

AF:

0.143

AC:

808

AN:

5663

Middle Eastern (MID)

AF:

0.265

AC:

AN:

211

European-Non Finnish (NFE)

AF:

0.232

AC:

12172

AN:

52560

Other (OTH)

AF:

0.174

AC:

262

AN:

1510

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

495

990

1485

1980

2475

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

328

492

656

820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.146

Hom.:

1198

Bravo

AF:

0.148

Asia WGS

AF:

0.0370

AC:

AN:

2519

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.50

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over