Genetic Variant LGALS3:p.Pro64His (chr14-55138217-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002306.4(LGALS3):c.191C>A(p.Pro64His) variant causes a missense change. The variant allele was found at a frequency of 0.389 in 1,613,016 control chromosomes in the GnomAD database, including 125,766 homozygotes. In-silico tool predicts 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.36 ( 10258 hom., cov: 32)

Exomes 𝑓: 0.39 ( 115508 hom. )

Consequence

LGALS3
NM_002306.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.61

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]

LGALS3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030170083).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGALS3	NM_002306.4 link	c.191C>A	p.Pro64His	missense_variant	Exon 3 of 6	ENST00000254301.14	NP_002297.2	P17931A0A024R693
LGALS3	NM_001357678.2 link	c.233C>A	p.Pro78His	missense_variant	Exon 4 of 7		NP_001344607.1
LGALS3	NR_003225.2 link	n.1235C>A		non_coding_transcript_exon_variant	Exon 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LGALS3	ENST00000254301.14 link	c.191C>A	p.Pro64His	missense_variant	Exon 3 of 6	1	NM_002306.4	ENSP00000254301.9		P17931

Frequencies

GnomAD3 genomes

AF:

0.357

AC:

54259

AN:

151874

Hom.:

10247

Cov.:

show subpopulations

Gnomad AFR

AF:

0.280

Gnomad AMI

AF:

0.417

Gnomad AMR

AF:

0.305

Gnomad ASJ

AF:

0.259

Gnomad EAS

AF:

0.206

Gnomad SAS

AF:

0.355

Gnomad FIN

AF:

0.529

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.406

Gnomad OTH

AF:

0.327

GnomAD3 exomes

AF:

0.351

AC:

86468

AN:

246424

Hom.:

16543

AF XY:

0.358

AC XY:

48072

AN XY:

134418

show subpopulations

Gnomad AFR exome

AF:

0.272

Gnomad AMR exome

AF:

0.215

Gnomad ASJ exome

AF:

0.263

Gnomad EAS exome

AF:

0.192

Gnomad SAS exome

AF:

0.369

Gnomad FIN exome

AF:

0.514

Gnomad NFE exome

AF:

0.400

Gnomad OTH exome

AF:

0.352

GnomAD4 exome

AF:

0.393

AC:

573600

AN:

1461024

Hom.:

115508

Cov.:

AF XY:

0.392

AC XY:

284784

AN XY:

726828

show subpopulations

Gnomad4 AFR exome

AF:

0.271

Gnomad4 AMR exome

AF:

0.224

Gnomad4 ASJ exome

AF:

0.269

Gnomad4 EAS exome

AF:

0.222

Gnomad4 SAS exome

AF:

0.376

Gnomad4 FIN exome

AF:

0.515

Gnomad4 NFE exome

AF:

0.409

Gnomad4 OTH exome

AF:

0.373

GnomAD4 genome

AF:

0.357

AC:

54298

AN:

151992

Hom.:

10258

Cov.:

AF XY:

0.360

AC XY:

26770

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.280

Gnomad4 AMR

AF:

0.305

Gnomad4 ASJ

AF:

0.259

Gnomad4 EAS

AF:

0.206

Gnomad4 SAS

AF:

0.356

Gnomad4 FIN

AF:

0.529

Gnomad4 NFE

AF:

0.407

Gnomad4 OTH

AF:

0.325

Alfa

AF:

0.369

Hom.:

22698

Bravo

AF:

0.332

TwinsUK

AF:

0.407

AC:

1509

ALSPAC

AF:

0.408

AC:

1573

ESP6500AA

AF:

0.279

AC:

1015

ESP6500EA

AF:

0.398

AC:

3240

ExAC

AF:

0.351

AC:

42334

Asia WGS

AF:

0.289

AC:

1005

AN:

3478

EpiCase

AF:

0.378

EpiControl

AF:

0.369

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.21

T;T;T

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.57

T;T;T

MetaRNN

Benign

0.0030

T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.7

.;M;.

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-8.0

D;D;D

REVEL

Benign

0.18

Sift

Benign

0.052

T;D;D

Sift4G

Pathogenic

0.0

D;T;D

Polyphen

1.0

.;D;.

Vest4

0.37, 0.25

MPC

0.069

ClinPred

0.11

GERP RS

5.7

Varity_R

0.34

gMVP

0.77

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over