NM_153451.3:c.383T>C

Variant names:

• chr11-69667550-A-G
• NM_153451.3:c.383T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153451.3(LTO1):​c.383T>C​(p.Ile128Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LTO1 NM_153451.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.14
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.081992835).

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.383T>C	p.Ile128Thr	missense	Exon 5 of 5	NP_703152.1	Q8WV07

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTO1	ENST00000279147.9	TSL:1 MANE Select	c.383T>C	p.Ile128Thr	missense	Exon 5 of 5	ENSP00000279147.5	Q8WV07
	LTO1	ENST00000536870.5	TSL:1	c.206T>C	p.Ile69Thr	missense	Exon 3 of 3	ENSP00000441984.1	F5GWS9
	LTO1	ENST00000538554.6	TSL:2	c.345+345T>C		intron	N/A	ENSP00000446428.3	B4DFA5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.0	T
PhyloP100		4.1
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.092
Sift	Uncertain	0.024	D
Sift4G	Benign	0.16	T
Polyphen		0.097	B
Vest4		0.20
MutPred		0.31		Loss of sheet (P = 0.0126)
MVP		0.35
MPC		0.099
ClinPred		0.58	D
GERP RS		3.7
PromoterAI		0.0064	Neutral
Varity_R		0.10
gMVP		0.036
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

hg19: chr11-69482318;