Variant 11-69673271-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_153451.3(LTO1):c.101G>T(p.Gly34Val) variant causes a missense change. The variant allele was found at a frequency of 0.000128 in 1,613,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

LTO1
NM_153451.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.47

Variant links:

Genes affected

LTO1 (HGNC:17589): (LTO1 maturation factor of ABCE1) Involved in protein maturation by [4Fe-4S] cluster transfer; ribosomal large subunit biogenesis; and translational initiation. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

LTO1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.84

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTO1	NM_153451.3 linkuse as main transcript	c.101G>T	p.Gly34Val	missense_variant	2/5	ENST00000279147.9
LTO1	XM_006718470.4 linkuse as main transcript	c.101G>T	p.Gly34Val	missense_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTO1	ENST00000279147.9 linkuse as main transcript	c.101G>T	p.Gly34Val	missense_variant	2/5	1	NM_153451.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000163

AC:

AN:

251496

Hom.:

AF XY:

0.000162

AC XY:

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000752

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.0000791

Gnomad OTH exome

AF:

0.000814

GnomAD4 exome

AF:

0.000127

AC:

186

AN:

1461620

Hom.:

Cov.:

AF XY:

0.000129

AC XY:

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000805

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:

0.000126

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.000138

AC:

AN:

152334

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000224

Hom.:

Bravo

AF:

0.000283

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000165

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2021

The c.101G>T (p.G34V) alteration is located in exon 2 (coding exon 2) of the ORAOV1 gene. This alteration results from a G to T substitution at nucleotide position 101, causing the glycine (G) at amino acid position 34 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.78

BayesDel_addAF

Uncertain

0.089

BayesDel_noAF

Pathogenic

0.26

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.42

T;T;T;T;.

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.93

D;.;D;D;D

M_CAP

Benign

0.065

MetaRNN

Pathogenic

0.84

D;D;D;D;D

MetaSVM

Uncertain

0.10

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.61

PROVEAN

Pathogenic

-8.4

D;D;D;D;D

REVEL

Uncertain

0.57

Sift

Pathogenic

0.0

D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D

Polyphen

1.0

D;D;D;.;D

Vest4

0.91

MVP

0.86

MPC

0.48

ClinPred

0.91

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.78

gMVP

0.43

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over