NM_153451.3:c.353C>A

Variant names:

• chr11-69667580-G-T
• NM_153451.3:c.353C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_153451.3(LTO1):​c.353C>A​(p.Ser118*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000689 in 1,451,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LTO1 NM_153451.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.78

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.353C>A	p.Ser118*	stop_gained	Exon 5 of 5	ENST00000279147.9	NP_703152.1
LTO1	XM_006718470.4	c.353C>A	p.Ser118*	stop_gained	Exon 5 of 6		XP_006718533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTO1	ENST00000279147.9	c.353C>A	p.Ser118*	stop_gained	Exon 5 of 5	1	NM_153451.3	ENSP00000279147.5
LTO1	ENST00000538554.6	c.345+315C>A		intron_variant	Intron 4 of 6	2		ENSP00000446428.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451218 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 722618

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: 0.0000116

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
BayesDel_addAF	Pathogenic	0.53	D
BayesDel_noAF	Pathogenic	0.53
CADD	Pathogenic	42
DANN	Uncertain	1.0
Eigen	Pathogenic	0.80
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.97	D
Vest4		0.26
GERP RS		5.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.40		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.40		Position offset: 7

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: chr11-69482348;