14-55140300-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002306.4(LGALS3):​c.368C>T​(p.Pro123Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)

Consequence

LGALS3
NM_002306.4 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.76
Variant links:
Genes affected
LGALS3 (HGNC:6563): (galectin 3) This gene encodes a member of the galectin family of carbohydrate binding proteins. Members of this protein family have an affinity for beta-galactosides. The encoded protein is characterized by an N-terminal proline-rich tandem repeat domain and a single C-terminal carbohydrate recognition domain. This protein can self-associate through the N-terminal domain allowing it to bind to multivalent saccharide ligands. This protein localizes to the extracellular matrix, the cytoplasm and the nucleus. This protein plays a role in numerous cellular functions including apoptosis, innate immunity, cell adhesion and T-cell regulation. The protein exhibits antimicrobial activity against bacteria and fungi. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Oct 2014]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3055365).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LGALS3NM_002306.4 linkc.368C>T p.Pro123Leu missense_variant Exon 4 of 6 ENST00000254301.14 NP_002297.2 P17931A0A024R693
LGALS3NM_001357678.2 linkc.410C>T p.Pro137Leu missense_variant Exon 5 of 7 NP_001344607.1
LGALS3NR_003225.2 linkn.1412C>T non_coding_transcript_exon_variant Exon 2 of 4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LGALS3ENST00000254301.14 linkc.368C>T p.Pro123Leu missense_variant Exon 4 of 6 1 NM_002306.4 ENSP00000254301.9 P17931

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
29
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
Sep 12, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.368C>T (p.P123L) alteration is located in exon 4 (coding exon 3) of the LGALS3 gene. This alteration results from a C to T substitution at nucleotide position 368, causing the proline (P) at amino acid position 123 to be replaced by a leucine (L). 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
0.20
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.43
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.24
T;T
Eigen
Benign
0.053
Eigen_PC
Benign
0.045
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.82
T;T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.31
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.8
L;.
PrimateAI
Benign
0.39
T
PROVEAN
Pathogenic
-6.2
D;D
REVEL
Benign
0.15
Sift
Uncertain
0.010
D;T
Sift4G
Benign
0.24
T;T
Polyphen
0.80
P;.
Vest4
0.33
MutPred
0.58
Loss of glycosylation at P123 (P = 0.0414);Loss of glycosylation at P123 (P = 0.0414);
MVP
0.085
MPC
0.35
ClinPred
0.98
D
GERP RS
3.9
Varity_R
0.55
gMVP
0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-55607018; API