X-38367358-A-T

Variant names:

• chrX-38367358-A-T
• NM_000531.6:c.145A>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000531.6(OTC):​c.145A>T​(p.Thr49Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: OTC NM_000531.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.43

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]

ENSG00000250349 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTC	NM_000531.6	c.145A>T	p.Thr49Ser	missense_variant	Exon 2 of 10	ENST00000039007.5	NP_000522.3
OTC	NM_001407092.1	c.145A>T	p.Thr49Ser	missense_variant	Exon 4 of 12		NP_001394021.1
OTC	XM_017029556.2	c.145A>T	p.Thr49Ser	missense_variant	Exon 2 of 9		XP_016885045.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTC	ENST00000039007.5	c.145A>T	p.Thr49Ser	missense_variant	Exon 2 of 10	1	NM_000531.6	ENSP00000039007.4
ENSG00000250349	ENST00000465127.1	c.172-298763A>T		intron_variant	Intron 3 of 8	5		ENSP00000417050.1
OTC	ENST00000488812.1	n.237A>T		non_coding_transcript_exon_variant	Exon 2 of 6	5
OTC	ENST00000643344.1	n.145A>T		non_coding_transcript_exon_variant	Exon 2 of 11			ENSP00000496606.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Ornithine carbamoyltransferase deficiency Uncertain:1

May 24, 2023

Revvity Omics, Revvity

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	17
DANN	Benign	0.94
DEOGEN2	Uncertain	0.67	D
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.69	T
M_CAP	Pathogenic	0.42	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Uncertain	0.45	D
MutationAssessor	Benign	0.39	N
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.070	N
REVEL	Uncertain	0.44
Sift	Benign	0.67	T
Sift4G	Benign	0.86	T
Polyphen		0.0010	B
Vest4		0.46
MutPred		0.55		Loss of ubiquitination at K46 (P = 0.1191);
MVP		0.76
MPC		0.34
ClinPred		0.46	T
GERP RS		5.4
Varity_R		0.27
gMVP		0.67

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-38226611;