NM_153451.3:c.71G>C

Variant names:

• chr11-69673301-C-G
• NM_153451.3:c.71G>C

Variant summary

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

The NM_153451.3(LTO1):​c.71G>C​(p.Arg24Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,972 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/20 in silico tools predict a benign 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 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.408

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.71G>C	p.Arg24Pro	missense_variant	Exon 2 of 5	ENST00000279147.9	NP_703152.1
LTO1	XM_006718470.4	c.71G>C	p.Arg24Pro	missense_variant	Exon 2 of 6		XP_006718533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTO1	ENST00000279147.9	c.71G>C	p.Arg24Pro	missense_variant	Exon 2 of 5	1	NM_153451.3	ENSP00000279147.5
LTO1	ENST00000538554.6	c.71G>C	p.Arg24Pro	missense_variant	Exon 2 of 7	2		ENSP00000446428.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457972 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 725598

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: 9.02e-7

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	Pathogenic	0.58
BayesDel_addAF	Benign	0.0075	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.047	T;T;T;T;.
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.63	D
LIST_S2	Uncertain	0.87	D;.;D;D;D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.48	T;T;T;T;T
MetaSVM	Benign	-0.88	T
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-2.8	D;D;D;D;D
REVEL	Benign	0.23
Sift	Uncertain	0.017	D;D;D;D;D
Sift4G	Uncertain	0.021	D;T;T;T;D
Polyphen		0.99	D;B;B;.;B
Vest4		0.61
MutPred		0.56		Gain of loop (P = 0.0435);Gain of loop (P = 0.0435);Gain of loop (P = 0.0435);Gain of loop (P = 0.0435);Gain of loop (P = 0.0435);
MVP		0.55
MPC		0.21
ClinPred		0.93	D
GERP RS		-2.0
Varity_R		0.67
gMVP		0.30

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: chr11-69488069;