rs72554348

Variant names:

• chrX-38369882-G-A
• rs72554348
• NM_000531.6:c.298+5G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-38369882-G-A
• chrX-38369882-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000531.6(OTC):​c.298+5G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: OTC NM_000531.6 splice_region, intron
• Scores: Splicing: ADA: 0.5840
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29
• Publications: 6 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTC	NM_000531.6	c.298+5G>A		splice_region_variant, intron_variant	Intron 3 of 9	ENST00000039007.5	NP_000522.3
OTC	NM_001407092.1	c.298+5G>A		splice_region_variant, intron_variant	Intron 5 of 11		NP_001394021.1
OTC	XM_017029556.2	c.298+5G>A		splice_region_variant, 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.298+5G>A		splice_region_variant, intron_variant	Intron 3 of 9	1	NM_000531.6	ENSP00000039007.4
ENSG00000250349	ENST00000465127.1	c.172-296239G>A		intron_variant	Intron 3 of 8	5		ENSP00000417050.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1039832 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 313636

African (AFR) AF: 0.00 AC: 0 AN: 25359

American (AMR) AF: 0.00 AC: 0 AN: 35110

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18988

East Asian (EAS) AF: 0.00 AC: 0 AN: 29925

South Asian (SAS) AF: 0.00 AC: 0 AN: 52751

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40424

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3994

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 789088

Other (OTH) AF: 0.00 AC: 0 AN: 44193

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	17
DANN	Benign	0.78
PhyloP100		1.3

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.58
dbscSNV1_RF	Benign	0.53
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.26		Position offset: -5

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

Other links and lift over

dbSNP: rs72554348; hg19: chrX-38229135;