chr11-69675199-G-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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.

• 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

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTO1	NM_153451.3	c.41C>T	p.Ala14Val	missense_variant	Exon 1 of 5	ENST00000279147.9	NP_703152.1
LTO1	XM_006718470.4	c.41C>T	p.Ala14Val	missense_variant	Exon 1 of 6		XP_006718533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTO1	ENST00000279147.9	c.41C>T	p.Ala14Val	missense_variant	Exon 1 of 5	1	NM_153451.3	ENSP00000279147.5
LTO1	ENST00000538554.6	c.41C>T	p.Ala14Val	missense_variant	Exon 1 of 7	2		ENSP00000446428.3

Frequencies

GnomAD3 genomes Cov.: 33

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

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: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;.;T;T;.
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.92	D;.;T;D;D;D
M_CAP	Benign	0.073	D
MetaRNN	Uncertain	0.48	T;T;T;T;T;T
MetaSVM	Benign	-0.87	T
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-2.0	N;N;N;N;N;N
REVEL	Benign	0.21
Sift	Benign	0.22	T;D;T;D;D;T
Sift4G	Benign	0.11	T;T;D;T;T;T
Polyphen		0.99	D;P;D;P;.;D
Vest4		0.56
MutPred		0.54		Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);
MVP		0.54
MPC		0.31
ClinPred		0.98	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.32
gMVP		0.037

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

LitVar

Other links and lift over

dbSNP: rs143278292; hg19: chr11-69489967;