Variant 11-8263348-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002315.3(LMO1):c.15C>A(p.Asp5Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000689 in 1,452,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

LMO1
NM_002315.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.27

Variant links:

Genes affected

LMO1 (HGNC:6641): (LIM domain only 1) This locus encodes a transcriptional regulator that contains two cysteine-rich LIM domains but lacks a DNA-binding domain. LIM domains may play a role in protein interactions; thus the encoded protein may regulate transcription by competitively binding to specific DNA-binding transcription factors. Alterations at this locus have been associated with acute lymphoblastic T-cell leukemia. Chromosomal rearrangements have been observed between this locus and at least two loci, the delta subunit of the T-cell antigen receptor gene and the LIM domain binding 1 gene. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2012]

LMO1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1653786).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LMO1	NM_002315.3 linkuse as main transcript	c.15C>A	p.Asp5Glu	missense_variant	1/4	ENST00000335790.8	NP_002306.1
LMO1	NM_001270428.2 linkuse as main transcript	c.22+5079C>A		intron_variant			NP_001257357.1
LMO1	NR_073006.2 linkuse as main transcript	n.531C>A		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMO1	ENST00000335790.8 linkuse as main transcript	c.15C>A	p.Asp5Glu	missense_variant	1/4	1	NM_002315.3	ENSP00000338207	A1	P25800-1
LMO1	ENST00000428101.6 linkuse as main transcript	c.22+5079C>A		intron_variant		1		ENSP00000404538	P4	P25800-2
LMO1	ENST00000524379.1 linkuse as main transcript	n.41C>A		non_coding_transcript_exon_variant	1/4	1
LMO1	ENST00000534484.1 linkuse as main transcript	c.-9+324C>A		intron_variant		5		ENSP00000435456

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1452324

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722772

show subpopulations

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 19, 2024

The c.15C>A (p.D5E) alteration is located in exon 1 (coding exon 1) of the LMO1 gene. This alteration results from a C to A substitution at nucleotide position 15, causing the aspartic acid (D) at amino acid position 5 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.13

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.096

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.72

M_CAP

Benign

0.038

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

MutationTaster

Benign

0.88

D;D;D

PROVEAN

Benign

-0.67

REVEL

Benign

0.093

Sift

Benign

0.26

Sift4G

Benign

0.26

Polyphen

0.0

Vest4

0.26

MutPred

0.19

Loss of helix (P = 0.0123);

MVP

0.39

MPC

0.30

ClinPred

0.56

GERP RS

5.2

Varity_R

0.15

gMVP

0.29

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over