dbSNP rs4652: LGALS3:p.Thr98Pro (chr14-55138318-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T98T) has been classified as Benign.

Frequency

Genomes: 𝑓 0.56 ( 26584 hom., cov: 32)

Exomes 𝑓: 0.44 ( 148893 hom. )

Consequence

LGALS3
NM_002306.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.14

Publications

86 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002306.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LGALS3	NM_002306.4	MANE Select	c.292A>C	p.Thr98Pro	missense	Exon 3 of 6	NP_002297.2	P17931
LGALS3	NM_001357678.2		c.334A>C	p.Thr112Pro	missense	Exon 4 of 7	NP_001344607.1
LGALS3	NR_003225.2		n.1336A>C		non_coding_transcript_exon	Exon 1 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LGALS3	ENST00000254301.14	TSL:1 MANE Select	c.292A>C	p.Thr98Pro	missense	Exon 3 of 6	ENSP00000254301.9	P17931
LGALS3	ENST00000556438.6	TSL:1	n.1131A>C		non_coding_transcript_exon	Exon 1 of 4
LGALS3	ENST00000947958.1		c.433A>C	p.Thr145Pro	missense	Exon 4 of 7	ENSP00000618017.1

Frequencies

GnomAD3 genomes

AF:

0.556

AC:

84503

AN:

151980

Hom.:

26525

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.446

AC:

107637

AN:

241330

AF XY:

0.443

show subpopulations

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 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.:

AF XY:

0.444

AC XY:

322025

AN XY:

725928

show subpopulations

African (AFR)

AF:

0.887

AC:

29668

AN:

33436

American (AMR)

AF:

0.319

AC:

14213

AN:

44500

Ashkenazi Jewish (ASJ)

AF:

0.377

AC:

9848

AN:

26098

East Asian (EAS)

AF:

0.431

AC:

17108

AN:

39672

South Asian (SAS)

AF:

0.473

AC:

40797

AN:

86200

European-Finnish (FIN)

AF:

0.524

AC:

27259

AN:

52012

Middle Eastern (MID)

AF:

0.374

AC:

2156

AN:

5762

European-Non Finnish (NFE)

AF:

0.432

AC:

480257

AN:

1111162

Other (OTH)

AF:

0.458

AC:

27648

AN:

60318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

18446

36893

55339

73786

92232

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14804

29608

44412

59216

74020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.556

AC:

84622

AN:

152098

Hom.:

26584

Cov.:

AF XY:

0.554

AC XY:

41233

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.871

AC:

36181

AN:

41534

American (AMR)

AF:

0.407

AC:

6220

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.376

AC:

1303

AN:

3470

East Asian (EAS)

AF:

0.405

AC:

2087

AN:

5156

South Asian (SAS)

AF:

0.472

AC:

2277

AN:

4828

European-Finnish (FIN)

AF:

0.537

AC:

5674

AN:

10570

Middle Eastern (MID)

AF:

0.401

AC:

118

AN:

294

European-Non Finnish (NFE)

AF:

0.432

AC:

29337

AN:

67934

Other (OTH)

AF:

0.487

AC:

1028

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1679

3358

5037

6716

8395

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

690

1380

2070

2760

3450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.443

Hom.:

28857

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.044

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.77

CADD

Benign

6.8

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.064

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0042

LIST_S2

Benign

0.019

MetaRNN

Benign

9.9e-7

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.9

PhyloP100

1.1

PrimateAI

Uncertain

0.54

PROVEAN

Benign

4.1

REVEL

Benign

0.053

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.049

MPC

0.077

ClinPred

0.00026

GERP RS

3.3

Varity_R

0.054

gMVP

0.31

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over