chrX-38381302-G-GTT

Variant names:

• chrX-38381302-G-GTT
• rs398122026
• NM_000531.6:c.299-35_299-34dupTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000531.6(OTC):​c.299-35_299-34dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., 0 hem., cov: 19)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: OTC NM_000531.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.498
• Publications: 0 publications found

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

ENSG00000250349 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTC	NM_000531.6	c.299-35_299-34dupTT		intron_variant	Intron 3 of 9	ENST00000039007.5	NP_000522.3
OTC	NM_001407092.1	c.299-35_299-34dupTT		intron_variant	Intron 5 of 11		NP_001394021.1
OTC	XM_017029556.2	c.299-35_299-34dupTT		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	c.299-40_299-39insTT		intron_variant	Intron 3 of 9	1	NM_000531.6	ENSP00000039007.4
ENSG00000250349	ENST00000465127.1	c.172-284819_172-284818insTT		intron_variant	Intron 3 of 8	5		ENSP00000417050.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 110244 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.00

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: 0 AN: 910299 Hom.: 0 Cov.: 15 AF XY: 0.00 AC XY: 0 AN XY: 258075

African (AFR) AF: 0.00 AC: 0 AN: 22088

American (AMR) AF: 0.00 AC: 0 AN: 30688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17645

East Asian (EAS) AF: 0.00 AC: 0 AN: 29098

South Asian (SAS) AF: 0.00 AC: 0 AN: 46154

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39623

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3697

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 681723

Other (OTH) AF: 0.00 AC: 0 AN: 39583

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 110244 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 32630

African (AFR) AF: 0.00 AC: 0 AN: 30481

American (AMR) AF: 0.00 AC: 0 AN: 10309

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2603

East Asian (EAS) AF: 0.00 AC: 0 AN: 3550

South Asian (SAS) AF: 0.00 AC: 0 AN: 2665

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5666

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 229

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52585

Other (OTH) AF: 0.00 AC: 0 AN: 1491

Alfa AF: 0.00 Hom.: 1198

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.50

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs398122026; hg19: chrX-38240555;