11-69667550-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 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. 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTO1	NM_153451.3	c.383T>C	p.Ile128Thr	missense_variant	5/5	ENST00000279147.9
LTO1	XM_006718470.4	c.383T>C	p.Ile128Thr	missense_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTO1	ENST00000279147.9	c.383T>C	p.Ile128Thr	missense_variant	5/5	1	NM_153451.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 10, 2022

The c.383T>C (p.I128T) alteration is located in exon 5 (coding exon 5) of the ORAOV1 gene. This alteration results from a T to C substitution at nucleotide position 383, causing the isoleucine (I) at amino acid position 128 to be replaced by a threonine (T). 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	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;.;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.69	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.082	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.77	D;N;N;N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.96	N;N;N
REVEL	Benign	0.092
Sift	Uncertain	0.024	D;D;D
Sift4G	Benign	0.16	T;T;T
Polyphen		0.097	B;P;B
Vest4		0.20
MutPred		0.31		Loss of sheet (P = 0.0126);.;Loss of sheet (P = 0.0126);
MVP		0.35
MPC		0.099
ClinPred		0.58	D
GERP RS		3.7
Varity_R		0.10
gMVP		0.036

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-69482318;