1-87340153-A-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_006769.4(LMO4):ā€‹c.440A>Gā€‹(p.Asn147Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 1,614,040 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000046 ( 0 hom., cov: 33)
Exomes š‘“: 0.000034 ( 0 hom. )

Consequence

LMO4
NM_006769.4 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.95
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.30669785).
BS2
High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LMO4NM_006769.4 linkc.440A>G p.Asn147Ser missense_variant 4/5 ENST00000370544.10 NP_006760.1 P61968
LMO4NM_001369491.1 linkc.440A>G p.Asn147Ser missense_variant 4/5 NP_001356420.1
LMO4XM_047432941.1 linkc.440A>G p.Asn147Ser missense_variant 5/6 XP_047288897.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LMO4ENST00000370544.10 linkc.440A>G p.Asn147Ser missense_variant 4/51 NM_006769.4 ENSP00000359575.4 P61968
LMO4ENST00000370542.1 linkc.440A>G p.Asn147Ser missense_variant 4/51 ENSP00000359573.1 P61968
LMO4ENST00000489303.1 linkn.675A>G non_coding_transcript_exon_variant 3/42

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152190
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000121
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000278
AC:
7
AN:
251458
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135902
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000342
AC:
50
AN:
1461850
Hom.:
0
Cov.:
31
AF XY:
0.0000385
AC XY:
28
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000315
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152190
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.000121
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000987
Hom.:
0
Bravo
AF:
0.0000567
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000247
AC:
3
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

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 submitterclinical testingAmbry GeneticsJun 16, 2023The c.440A>G (p.N147S) alteration is located in exon 4 (coding exon 3) of the LMO4 gene. This alteration results from a A to G substitution at nucleotide position 440, causing the asparagine (N) at amino acid position 147 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
0.061
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Benign
0.12
T;T
Eigen
Benign
-0.11
Eigen_PC
Benign
0.17
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.90
.;D
M_CAP
Benign
0.0029
T
MetaRNN
Benign
0.31
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.46
N;N
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
-0.50
N;N
REVEL
Benign
0.13
Sift
Benign
0.60
T;T
Sift4G
Benign
0.80
T;T
Polyphen
0.0010
B;B
Vest4
0.67
MVP
0.51
MPC
0.98
ClinPred
0.12
T
GERP RS
6.0
Varity_R
0.089
gMVP
0.52

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.

Other links and lift over

dbSNP: rs371290370; hg19: chr1-87805836; COSMIC: COSV105297739; COSMIC: COSV105297739; API