rs4652

Positions:

• chr14-55138318-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002306.4(LGALS3):​c.292A>C​(p.Thr98Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 1,611,258 control chromosomes in the GnomAD database, including 175,477 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.56 (26584 hom., cov: 32)
  • Exomes 𝑓: 0.44 (148893 hom.)
• Consequence: LGALS3 NM_002306.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14

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]

LGALS3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.901192E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGALS3	NM_002306.4	c.292A>C	p.Thr98Pro	missense_variant	3/6	ENST00000254301.14	NP_002297.2
LGALS3	NM_001357678.2	c.334A>C	p.Thr112Pro	missense_variant	4/7		NP_001344607.1
LGALS3	NR_003225.2	n.1336A>C		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGALS3	ENST00000254301.14	c.292A>C	p.Thr98Pro	missense_variant	3/6	1	NM_002306.4	ENSP00000254301.9

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84503 AN: 151980 Hom.: 26525 Cov.: 32

Gnomad AFR AF: 0.871

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.486

GnomAD3 exomes AF: 0.446 AC: 107637 AN: 241330 Hom.: 26001 AF XY: 0.443 AC XY: 58718 AN XY: 132498

Gnomad AFR exome AF: 0.877

Gnomad AMR exome AF: 0.307

Gnomad ASJ exome AF: 0.371

Gnomad EAS exome AF: 0.389

Gnomad SAS exome AF: 0.469

Gnomad FIN exome AF: 0.527

Gnomad NFE exome AF: 0.428

Gnomad OTH exome AF: 0.428

GnomAD4 exome AF: 0.445 AC: 648954 AN: 1459160 Hom.: 148893 Cov.: 42 AF XY: 0.444 AC XY: 322025 AN XY: 725928

Gnomad4 AFR exome AF: 0.887

Gnomad4 AMR exome AF: 0.319

Gnomad4 ASJ exome AF: 0.377

Gnomad4 EAS exome AF: 0.431

Gnomad4 SAS exome AF: 0.473

Gnomad4 FIN exome AF: 0.524

Gnomad4 NFE exome AF: 0.432

Gnomad4 OTH exome AF: 0.458

GnomAD4 genome AF: 0.556 AC: 84622 AN: 152098 Hom.: 26584 Cov.: 32 AF XY: 0.554 AC XY: 41233 AN XY: 74368

Gnomad4 AFR AF: 0.871

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.376

Gnomad4 EAS AF: 0.405

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.487

Alfa AF: 0.435 Hom.: 18606

Bravo AF: 0.555

TwinsUK AF: 0.434 AC: 1610

ALSPAC AF: 0.430 AC: 1657

ESP6500AA AF: 0.858 AC: 2923

ESP6500EA AF: 0.467 AC: 3644

ExAC AF: 0.450 AC: 53054

Asia WGS AF: 0.488 AC: 1694 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.044
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.8
DANN	Benign	0.69
DEOGEN2	Benign	0.064	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0042	N
LIST_S2	Benign	0.019	T;T
MetaRNN	Benign	9.9e-7	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.9	N;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	4.1	N;N
REVEL	Benign	0.053
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;.
Vest4		0.049
MPC		0.077
ClinPred		0.00026	T
GERP RS		3.3
Varity_R		0.054
gMVP		0.31

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: rs4652; hg19: chr14-55605036;