Variant 11-69667927-C-T 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.313G>A(p.Asp105Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000702 in 1,424,050 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: not found (cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

LTO1
NM_153451.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.59

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, 0.749

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTO1	NM_153451.3 link	c.313G>A	p.Asp105Asn	missense_variant	Exon 4 of 5	ENST00000279147.9	NP_703152.1	Q8WV07A0A024R5H3
LTO1	XM_006718470.4 link	c.313G>A	p.Asp105Asn	missense_variant	Exon 4 of 6		XP_006718533.1	Q8WV07A0A024R5H3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTO1	ENST00000279147.9 link	c.313G>A	p.Asp105Asn	missense_variant	Exon 4 of 5	1	NM_153451.3	ENSP00000279147.5		Q8WV07
LTO1	ENST00000538554.6 link	c.313G>A	p.Asp105Asn	missense_variant	Exon 4 of 7	2		ENSP00000446428.3		B4DFA5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251438

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.02e-7

AC:

AN:

1424050

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

710908

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.313G>A (p.D105N) alteration is located in exon 4 (coding exon 4) of the ORAOV1 gene. This alteration results from a G to A substitution at nucleotide position 313, causing the aspartic acid (D) at amino acid position 105 to be replaced by an asparagine (N). 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

0.22

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.11

T;T;.;T;T

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.94

D;.;D;D;D

M_CAP

Benign

0.028

MetaRNN

Pathogenic

0.75

D;D;D;D;D

MetaSVM

Benign

-0.72

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.7

D;D;D;D;D

REVEL

Benign

0.21

Sift

Uncertain

0.0090

D;D;D;D;D

Sift4G

Uncertain

0.015

D;T;D;T;T

Polyphen

0.99

D;P;D;P;.

Vest4

0.55

MutPred

0.82

Loss of ubiquitination at K108 (P = 0.0563);Loss of ubiquitination at K108 (P = 0.0563);.;Loss of ubiquitination at K108 (P = 0.0563);Loss of ubiquitination at K108 (P = 0.0563);

MVP

0.47

MPC

0.16

ClinPred

0.94

GERP RS

3.7

Varity_R

0.25

gMVP

0.19

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