Variant rs72554305 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The ENST00000039007.5(OTC):c.106C>G(p.Gln36Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000917 in 1,090,844 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 9.2e-7 ( 0 hom. 0 hem. )

Consequence

OTC
ENST00000039007.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.358

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1

In a hotspot region, there are 6 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 2 benign, 6 uncertain in ENST00000039007.5

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10743341).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
OTC	NM_000531.6 linkuse as main transcript	c.106C>G	p.Gln36Glu	missense_variant	2/10	ENST00000039007.5	NP_000522.3
OTC	NM_001407092.1 linkuse as main transcript	c.106C>G	p.Gln36Glu	missense_variant	4/12		NP_001394021.1
OTC	XM_017029556.2 linkuse as main transcript	c.106C>G	p.Gln36Glu	missense_variant	2/9		XP_016885045.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
OTC	ENST00000039007.5 linkuse as main transcript	c.106C>G	p.Gln36Glu	missense_variant	2/10	1	NM_000531.6	ENSP00000039007	P1
OTC	ENST00000488812.1 linkuse as main transcript	n.198C>G		non_coding_transcript_exon_variant	2/6	5
OTC	ENST00000643344.1 linkuse as main transcript	c.106C>G	p.Gln36Glu	missense_variant, NMD_transcript_variant	2/11			ENSP00000496606

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000547

AC:

AN:

182817

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67357

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.17e-7

AC:

AN:

1090844

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

356454

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.33

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.74

M_CAP

Uncertain

0.086

MetaRNN

Benign

0.11

MetaSVM

Uncertain

0.24

MutationAssessor

Benign

1.6

MutationTaster

Benign

0.99

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.43

REVEL

Uncertain

0.34

Sift

Benign

0.41

Sift4G

Benign

0.87

Polyphen

0.0030

Vest4

0.35

MutPred

0.36

Gain of ubiquitination at K34 (P = 0.039);

MVP

0.45

MPC

0.40

ClinPred

0.015

GERP RS

2.4

Varity_R

0.10

gMVP

0.83

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over