NM_000531.6:c.299-34dupT

Variant names:

• chrX-38381302-G-GT
• rs398122026
• NM_000531.6:c.299-34dupT

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.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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• 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: Orphanet, Laboratory for Molecular Medicine, ClinGen, G2P, Labcorp Genetics (formerly Invitae)

ENSG00000250349 (HGNC:):

ACMG classification

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.

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.299-34dupT		intron	N/A	NP_000522.3
	OTC	NM_001407092.1		c.299-34dupT		intron	N/A	NP_001394021.1	P00480

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTC	ENST00000039007.5	TSL:1 MANE Select	c.299-40_299-39insT		intron	N/A	ENSP00000039007.4	P00480
	ENSG00000250349	ENST00000465127.1	TSL:5	c.172-284819_172-284818insT		intron	N/A	ENSP00000417050.1	B4E171
	OTC	ENST00000713758.1		c.299-40_299-39insT		intron	N/A	ENSP00000519059.1	P00480

Frequencies

GnomAD3 genomes AF: 0.153 AC: 16831 AN: 110215 Hom.: 1384 Cov.: 19

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

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.: 15 AF XY: 0.190 AC XY: 48998 AN XY: 257999

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: 14 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

GnomAD4 genome AF: 0.153 AC: 16821 AN: 110264 Hom.: 1383 Cov.: 19 AF XY: 0.138 AC XY: 4501 AN XY: 32674

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: 2 AN: 3538

South Asian (SAS) AF: 0.0324 AC: 86 AN: 2654

European-Finnish (FIN) AF: 0.143 AC: 808 AN: 5663

Middle Eastern (MID) AF: 0.265 AC: 56 AN: 211

European-Non Finnish (NFE) AF: 0.232 AC: 12172 AN: 52560

Other (OTH) AF: 0.174 AC: 262 AN: 1510

Alfa AF: 0.146 Hom.: 1198

Bravo AF: 0.148

Asia WGS AF: 0.0370 AC: 96 AN: 2519

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs398122026; hg19: chrX-38240555;