14-55145228-C-T

Variant names:

• chr14-55145228-C-T
• rs1042869
• NM_002306.4:c.710C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002306.4(LGALS3):​c.710C>T​(p.Ser237Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: LGALS3 NM_002306.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.390

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]

ACMG classification

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=0.3421455).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGALS3	NM_002306.4	c.710C>T	p.Ser237Phe	missense_variant	Exon 6 of 6	ENST00000254301.14	NP_002297.2
LGALS3	NM_001357678.2	c.752C>T	p.Ser251Phe	missense_variant	Exon 7 of 7		NP_001344607.1
LGALS3	NR_003225.2	n.1754C>T		non_coding_transcript_exon_variant	Exon 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LGALS3	ENST00000254301.14	c.710C>T	p.Ser237Phe	missense_variant	Exon 6 of 6	1	NM_002306.4	ENSP00000254301.9
LGALS3	ENST00000556438.6	n.1549C>T		non_coding_transcript_exon_variant	Exon 4 of 4	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461782 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727198

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.710C>T (p.S237F) alteration is located in exon 6 (coding exon 5) of the LGALS3 gene. This alteration results from a C to T substitution at nucleotide position 710, causing the serine (S) at amino acid position 237 to be replaced by a phenylalanine (F). 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	0.30
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Benign	0.84
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.074
Sift	Benign	0.55	T
Sift4G	Benign	0.70	T
Polyphen		0.96	D
Vest4		0.26
MutPred		0.35		Loss of disorder (P = 0.0096);
MVP		0.34
MPC		0.19
ClinPred		0.19	T
GERP RS		1.9
Varity_R		0.26
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

LitVar

Other links and lift over

dbSNP: rs1042869; hg19: chr14-55611946;