11-69671809-T-G

Variant names:

• chr11-69671809-T-G
• rs769264502
• NM_153451.3:c.167A>C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_153451.3(LTO1):​c.167A>C​(p.Tyr56Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000419 in 1,433,280 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: 0.0000042 (0 hom.)
• Consequence: LTO1 NM_153451.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.25

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.977

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTO1	NM_153451.3	c.167A>C	p.Tyr56Ser	missense_variant	Exon 3 of 5	ENST00000279147.9	NP_703152.1
LTO1	XM_006718470.4	c.167A>C	p.Tyr56Ser	missense_variant	Exon 3 of 6		XP_006718533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTO1	ENST00000279147.9	c.167A>C	p.Tyr56Ser	missense_variant	Exon 3 of 5	1	NM_153451.3	ENSP00000279147.5
LTO1	ENST00000538554.6	c.167A>C	p.Tyr56Ser	missense_variant	Exon 3 of 7	2		ENSP00000446428.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251468 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135912

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000419 AC: 6 AN: 1433280 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 715072

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: 0.00000553

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.16
CADD	Uncertain	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.37	T;T;T;T;.
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.74	T;.;T;T;T
M_CAP	Benign	0.049	D
MetaRNN	Pathogenic	0.98	D;D;D;D;D
MetaSVM	Uncertain	-0.18	T
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-7.3	D;D;D;D;D
REVEL	Uncertain	0.52
Sift	Benign	0.064	T;T;T;T;T
Sift4G	Uncertain	0.056	T;T;T;T;T
Polyphen		0.91	P;D;D;.;D
Vest4		0.92
MutPred		0.88		Gain of disorder (P = 0.0308);Gain of disorder (P = 0.0308);Gain of disorder (P = 0.0308);Gain of disorder (P = 0.0308);Gain of disorder (P = 0.0308);
MVP		0.75
MPC		0.47
ClinPred		0.97	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.60
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs769264502; hg19: chr11-69486577;