rs55722856

Variant names:

• chrX-38408862-T-C
• rs55722856
• NM_000531.6:c.718-14T>C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000531.6(OTC):​c.718-14T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 1,208,527 control chromosomes in the GnomAD database, including 879 homozygotes. There are 3,338 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.054 (461 hom., 1564 hem., cov: 22)
  • Exomes 𝑓: 0.0061 (418 hom. 1774 hem.)
• Consequence: OTC NM_000531.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.512
• Publications: 3 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: Benign. The variant received -16 ACMG points.

• BP6: Variant X-38408862-T-C is Benign according to our data. Variant chrX-38408862-T-C is described in ClinVar as Benign. ClinVar VariationId is 93223.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000531.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTC	NM_000531.6	MANE Select	c.718-14T>C		intron	N/A	NP_000522.3
	OTC	NM_001407092.1		c.718-14T>C		intron	N/A	NP_001394021.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTC	ENST00000039007.5	TSL:1 MANE Select	c.718-14T>C		intron	N/A	ENSP00000039007.4
	ENSG00000250349	ENST00000465127.1	TSL:5	c.172-257259T>C		intron	N/A	ENSP00000417050.1
	OTC	ENST00000713758.1		c.718-14T>C		intron	N/A	ENSP00000519059.1

Frequencies

GnomAD3 genomes AF: 0.0541 AC: 6011 AN: 111052 Hom.: 461 Cov.: 22

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00844

Gnomad SAS AF: 0.000766

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000528

Gnomad OTH AF: 0.0301

GnomAD2 exomes AF: 0.0168 AC: 3081 AN: 183273 AF XY: 0.0107

Gnomad AFR exome AF: 0.197

Gnomad AMR exome AF: 0.00974

Gnomad ASJ exome AF: 0.000134

Gnomad EAS exome AF: 0.00888

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000379

Gnomad OTH exome AF: 0.00796

GnomAD4 exome AF: 0.00607 AC: 6663 AN: 1097423 Hom.: 418 Cov.: 30 AF XY: 0.00489 AC XY: 1774 AN XY: 362805

African (AFR) AF: 0.195 AC: 5157 AN: 26385

American (AMR) AF: 0.0103 AC: 364 AN: 35204

Ashkenazi Jewish (ASJ) AF: 0.0000516 AC: 1 AN: 19378

East Asian (EAS) AF: 0.00394 AC: 119 AN: 30194

South Asian (SAS) AF: 0.00187 AC: 101 AN: 54132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40533

Middle Eastern (MID) AF: 0.00459 AC: 19 AN: 4135

European-Non Finnish (NFE) AF: 0.000240 AC: 202 AN: 841388

Other (OTH) AF: 0.0152 AC: 700 AN: 46074

GnomAD4 genome AF: 0.0543 AC: 6034 AN: 111104 Hom.: 461 Cov.: 22 AF XY: 0.0469 AC XY: 1564 AN XY: 33328

African (AFR) AF: 0.189 AC: 5752 AN: 30402

American (AMR) AF: 0.0169 AC: 176 AN: 10444

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2643

East Asian (EAS) AF: 0.00847 AC: 30 AN: 3541

South Asian (SAS) AF: 0.000769 AC: 2 AN: 2602

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6004

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.000528 AC: 28 AN: 53051

Other (OTH) AF: 0.0304 AC: 46 AN: 1513

Alfa AF: 0.0447 Hom.: 582

Bravo AF: 0.0639

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Ornithine carbamoyltransferase deficiency (4)
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.52
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.25		Position offset: 14

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

Other links and lift over

dbSNP: rs55722856; hg19: chrX-38268115;