Genetic Variant NM_153451.3:c.5C>T (chr11-69675235-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_153451.3(LTO1):c.5C>T(p.Ala2Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000739 in 1,352,284 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A2G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

LTO1
NM_153451.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.55

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM1

In a modified_residue N-acetylalanine (size 0) in uniprot entity LTO1_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26225916).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153451.3. 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
	LTO1	NM_153451.3	MANE Select	c.5C>T	p.Ala2Val	missense	Exon 1 of 5	NP_703152.1	Q8WV07

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LTO1	ENST00000279147.9	TSL:1 MANE Select	c.5C>T	p.Ala2Val	missense	Exon 1 of 5	ENSP00000279147.5	Q8WV07
LTO1	ENST00000538554.6	TSL:2	c.5C>T	p.Ala2Val	missense	Exon 1 of 7	ENSP00000446428.3	B4DFA5
LTO1	ENST00000536870.5	TSL:1	c.5C>T	p.Ala2Val	missense	Exon 1 of 3	ENSP00000441984.1	F5GWS9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000641

AC:

AN:

156098

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000129

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.39e-7

AC:

AN:

1352284

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

662962

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28378

American (AMR)

AF:

0.00

AC:

AN:

27162

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19894

East Asian (EAS)

AF:

0.00

AC:

AN:

36198

South Asian (SAS)

AF:

0.00

AC:

AN:

70072

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49560

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5296

European-Non Finnish (NFE)

AF:

9.43e-7

AC:

AN:

1060338

Other (OTH)

AF:

0.00

AC:

AN:

55386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.825

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000831

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

0.0038

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.024

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.62

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.82

PhyloP100

5.6

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.8

REVEL

Benign

0.12

Sift

Uncertain

0.023

Sift4G

Uncertain

0.013

Polyphen

0.99

Vest4

0.44

MutPred

0.30

Loss of disorder (P = 0.0957)

MVP

0.47

MPC

0.24

ClinPred

0.91

GERP RS

3.8

PromoterAI

-0.048

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.13

gMVP

0.041

Mutation Taster

=83/17

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over