15-51887648-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_014547.5(TMOD3):​c.343C>G​(p.Leu115Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

TMOD3
NM_014547.5 missense

Scores

3
6
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.72

Publications

0 publications found
Variant links:
Genes affected
TMOD3 (HGNC:11873): (tropomodulin 3) Enables cadherin binding activity involved in cell-cell adhesion. Predicted to be involved in actin filament organization; muscle contraction; and myofibril assembly. Predicted to act upstream of or within actin cytoskeleton organization; erythrocyte development; and positive regulation of mitotic cell cycle phase transition. Located in adherens junction. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.37528247).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMOD3NM_014547.5 linkc.343C>G p.Leu115Val missense_variant Exon 4 of 10 ENST00000308580.12 NP_055362.1 Q9NYL9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMOD3ENST00000308580.12 linkc.343C>G p.Leu115Val missense_variant Exon 4 of 10 1 NM_014547.5 ENSP00000308753.7 Q9NYL9

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 16, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.343C>G (p.L115V) alteration is located in exon 4 (coding exon 3) of the TMOD3 gene. This alteration results from a C to G substitution at nucleotide position 343, causing the leucine (L) at amino acid position 115 to be replaced by a valine (V). 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
0.21
BayesDel_addAF
Benign
-0.0097
T
BayesDel_noAF
Benign
-0.25
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.41
T
Eigen
Pathogenic
0.82
Eigen_PC
Pathogenic
0.77
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.92
D
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.38
T
MetaSVM
Benign
-0.40
T
MutationAssessor
Uncertain
2.6
M
PhyloP100
4.7
PrimateAI
Uncertain
0.49
T
PROVEAN
Uncertain
-2.5
N
REVEL
Benign
0.22
Sift
Uncertain
0.025
D
Sift4G
Benign
0.12
T
Polyphen
1.0
D
Vest4
0.28
MutPred
0.63
Loss of loop (P = 0.0203);
MVP
0.42
MPC
0.12
ClinPred
0.86
D
GERP RS
5.6
Varity_R
0.33
gMVP
0.36
Mutation Taster
=73/27
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

hg19: chr15-52179845; API