chr11-69675199-G-A

Variant names:

• chr11-69675199-G-A
• rs143278292
• NM_153451.3:c.41C>T

Variant summary

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

The NM_153451.3(LTO1):​c.41C>T​(p.Ala14Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. A14E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LTO1 NM_153451.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.06
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.41C>T	p.Ala14Val	missense	Exon 1 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.41C>T	p.Ala14Val	missense	Exon 1 of 5	ENSP00000279147.5	Q8WV07
	LTO1	ENST00000538554.6	TSL:2	c.41C>T	p.Ala14Val	missense	Exon 1 of 7	ENSP00000446428.3	B4DFA5
	LTO1	ENST00000536870.5	TSL:1	c.41C>T	p.Ala14Val	missense	Exon 1 of 3	ENSP00000441984.1	F5GWS9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 193998 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1409528 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 698944

African (AFR) AF: 0.00 AC: 0 AN: 30708

American (AMR) AF: 0.00 AC: 0 AN: 32364

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22508

East Asian (EAS) AF: 0.00 AC: 0 AN: 38966

South Asian (SAS) AF: 0.00 AC: 0 AN: 78286

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51148

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5480

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1092286

Other (OTH) AF: 0.00 AC: 0 AN: 57782

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.073	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.87	T
PhyloP100		6.1
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.21
Sift	Benign	0.22	T
Sift4G	Benign	0.11	T
Polyphen		0.99	D
Vest4		0.56
MutPred		0.54		Gain of sheet (P = 0.0149)
MVP		0.54
MPC		0.31
ClinPred		0.98	D
GERP RS		4.1
PromoterAI		-0.081	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.32
gMVP		0.037
Mutation Taster		=73/27	polymorphism

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

Other links and lift over

dbSNP: rs143278292; hg19: chr11-69489967;