Variant 1-87332106-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_006769.4(LMO4):c.91G>T(p.Ala31Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,613,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

LMO4
NM_006769.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.12

Variant links:

Genes affected

LMO4 (HGNC:6644): (LIM domain only 4) This gene encodes a cysteine-rich protein that contains two LIM domains but lacks a DNA-binding homeodomain. The encoded protein may play a role as a transcriptional regulator or as an oncogene. [provided by RefSeq, Aug 2008]

LMO4 links:

LMO4 (HGNC:):

LMO4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.24319425).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMO4	NM_006769.4 linkuse as main transcript	c.91G>T	p.Ala31Ser	missense_variant	2/5	ENST00000370544.10	NP_006760.1	P61968
LMO4	NM_001369491.1 linkuse as main transcript	c.91G>T	p.Ala31Ser	missense_variant	2/5		NP_001356420.1
LMO4	XM_047432941.1 linkuse as main transcript	c.91G>T	p.Ala31Ser	missense_variant	3/6		XP_047288897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LMO4	ENST00000370544.10 linkuse as main transcript	c.91G>T	p.Ala31Ser	missense_variant	2/5	1	NM_006769.4	ENSP00000359575.4	P61968
LMO4	ENST00000370542.1 linkuse as main transcript	c.91G>T	p.Ala31Ser	missense_variant	2/5	1		ENSP00000359573.1	P61968
LMO4	ENST00000489303.1 linkuse as main transcript	n.326G>T		non_coding_transcript_exon_variant	1/4	2
LMO4	ENST00000495705.5 linkuse as main transcript	n.323G>T		non_coding_transcript_exon_variant	3/4	3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461758

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000162

Hom.:

Bravo

AF:

0.00000378

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

Apr 13, 2022

The c.91G>T (p.A31S) alteration is located in exon 2 (coding exon 1) of the LMO4 gene. This alteration results from a G to T substitution at nucleotide position 91, causing the alanine (A) at amino acid position 31 to be replaced by a serine (S). 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

0.099

BayesDel_addAF

Uncertain

0.037

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Benign

0.95

DEOGEN2

Benign

0.24

T;T

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.092

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.88

.;D

M_CAP

Benign

0.0059

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

-0.11

N;N

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.060

N;N

REVEL

Benign

0.29

Sift

Benign

0.74

T;T

Sift4G

Benign

0.80

T;T

Polyphen

0.0010

B;B

Vest4

0.25

MutPred

0.34

Gain of MoRF binding (P = 0.1387);Gain of MoRF binding (P = 0.1387);

MVP

0.64

MPC

1.1

ClinPred

0.91

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.34

gMVP

0.36

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

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