dbSNP rs5917586: OTC:c.299-18C>A (chrX-38381324-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000531.6(OTC):c.299-18C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000188 in 106,590 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000019 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

OTC
NM_000531.6 intron

Scores

Clinical Significance

Not reported in ClinVar

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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
OTC	NM_000531.6 link	c.299-18C>A	intron_variant	Intron 3 of 9	ENST00000039007.5	NP_000522.3	P00480
OTC	NM_001407092.1 link	c.299-18C>A	intron_variant	Intron 5 of 11		NP_001394021.1
OTC	XM_017029556.2 link	c.299-18C>A	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>A		intron_variant	Intron 3 of 9	1	NM_000531.6	ENSP00000039007.4		P00480
ENSG00000250349	ENST00000465127.1 link	c.172-284797C>A		intron_variant	Intron 3 of 8	5		ENSP00000417050.1		B4E171

Frequencies

GnomAD3 genomes

AF:

0.0000188

AC:

AN:

106590

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000682

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

832850

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

259792

African (AFR)

AF:

0.00

AC:

AN:

19342

American (AMR)

AF:

0.00

AC:

AN:

26021

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15165

East Asian (EAS)

AF:

0.00

AC:

AN:

23106

South Asian (SAS)

AF:

0.00

AC:

AN:

39218

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33916

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3440

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

637588

Other (OTH)

AF:

0.00

AC:

AN:

35054

GnomAD4 genome

AF:

0.0000188

AC:

AN:

106590

Hom.:

Cov.:

AF XY:

0.0000327

AC XY:

AN XY:

30550

show subpopulations

African (AFR)

AF:

0.0000682

AC:

AN:

29340

American (AMR)

AF:

0.00

AC:

AN:

9879

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2570

East Asian (EAS)

AF:

0.00

AC:

AN:

3414

South Asian (SAS)

AF:

0.00

AC:

AN:

2468

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5071

Middle Eastern (MID)

AF:

0.00

AC:

AN:

231

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

51528

Other (OTH)

AF:

0.00

AC:

AN:

1430

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.061

(source)

DANN

Benign

0.28

PhyloP100

-3.2

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over