Variant 11-69673301-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_153451.3(LTO1):c.71G>A(p.Arg24Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,610,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

LTO1
NM_153451.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.408

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04137364).

BP6

Variant 11-69673301-C-T is Benign according to our data. Variant chr11-69673301-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2517923.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTO1	NM_153451.3 link	c.71G>A	p.Arg24Gln	missense_variant	Exon 2 of 5	ENST00000279147.9	NP_703152.1	Q8WV07A0A024R5H3
LTO1	XM_006718470.4 link	c.71G>A	p.Arg24Gln	missense_variant	Exon 2 of 6		XP_006718533.1	Q8WV07A0A024R5H3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTO1	ENST00000279147.9 link	c.71G>A	p.Arg24Gln	missense_variant	Exon 2 of 5	1	NM_153451.3	ENSP00000279147.5		Q8WV07
LTO1	ENST00000538554.6 link	c.71G>A	p.Arg24Gln	missense_variant	Exon 2 of 7	2		ENSP00000446428.3		B4DFA5

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000278

AC:

AN:

251464

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

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:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000206

AC:

AN:

1457972

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

725598

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000244

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

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:

0.0000329

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Apr 11, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.55

DEOGEN2

Benign

0.0035

T;T;T;T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.80

T;.;T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.041

T;T;T;T;T

MetaSVM

Benign

-0.95

PrimateAI

Benign

0.33

PROVEAN

Benign

0.87

N;N;N;N;N

REVEL

Benign

0.041

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

0.33

T;T;T;T;T

Polyphen

0.24

B;B;B;.;B

Vest4

0.24

MVP

0.24

MPC

0.085

ClinPred

0.029

GERP RS

-2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.029

gMVP

0.015

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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