13-75713189-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001306080.2(LMO7):​c.77C>A​(p.Thr26Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000223 in 1,611,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

LMO7
NM_001306080.2 missense

Scores

10
6
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.23
Variant links:
Genes affected
LMO7 (HGNC:6646): (LIM domain 7) This gene encodes a protein containing a calponin homology (CH) domain, a PDZ domain, and a LIM domain, and may be involved in protein-protein interactions. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene, however, the full-length nature of some variants is not known. [provided by RefSeq, Jan 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.82

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LMO7NM_001306080.2 linkc.77C>A p.Thr26Lys missense_variant Exon 2 of 31 ENST00000377534.8 NP_001293009.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LMO7ENST00000377534.8 linkc.77C>A p.Thr26Lys missense_variant Exon 2 of 31 1 NM_001306080.2 ENSP00000366757.4 F8WD26

Frequencies

GnomAD3 genomes
AF:
0.000105
AC:
16
AN:
152134
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00105
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000678
AC:
17
AN:
250598
Hom.:
0
AF XY:
0.0000517
AC XY:
7
AN XY:
135488
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000495
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000137
AC:
20
AN:
1459656
Hom.:
0
Cov.:
29
AF XY:
0.0000138
AC XY:
10
AN XY:
726230
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000450
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.000105
AC:
16
AN:
152134
Hom.:
0
Cov.:
32
AF XY:
0.000148
AC XY:
11
AN XY:
74298
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00105
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000132

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 05, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.233C>A (p.T78K) alteration is located in exon 3 (coding exon 3) of the LMO7 gene. This alteration results from a C to A substitution at nucleotide position 233, causing the threonine (T) at amino acid position 78 to be replaced by a lysine (K). 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
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.50
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.79
D;.;.;D
Eigen
Pathogenic
0.83
Eigen_PC
Pathogenic
0.74
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.90
D;D;D;D
M_CAP
Benign
0.064
D
MetaRNN
Pathogenic
0.82
D;D;D;D
MetaSVM
Pathogenic
0.99
D
MutationAssessor
Pathogenic
3.7
.;H;.;.
PrimateAI
Uncertain
0.71
T
PROVEAN
Pathogenic
-4.6
.;D;D;.
REVEL
Pathogenic
0.70
Sift
Uncertain
0.0010
.;D;D;.
Sift4G
Pathogenic
0.0
D;D;D;D
Polyphen
1.0
.;D;.;.
Vest4
0.89
MVP
0.97
ClinPred
0.90
D
GERP RS
5.6
gMVP
0.80

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: rs796774332; hg19: chr13-76287325; API