Genetic Variant NM_002306.4:c.191C>A (chr14-55138217-C-A) – 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.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.

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

Publications

107 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=0.0030170083).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.403 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.191C>A	p.Pro64His	missense	Exon 3 of 6	NP_002297.2	P17931
LGALS3	NM_001357678.2		c.233C>A	p.Pro78His	missense	Exon 4 of 7	NP_001344607.1
LGALS3	NR_003225.2		n.1235C>A		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.191C>A	p.Pro64His	missense	Exon 3 of 6	ENSP00000254301.9	P17931
LGALS3	ENST00000556438.6	TSL:1	n.1030C>A		non_coding_transcript_exon	Exon 1 of 4
LGALS3	ENST00000947958.1		c.332C>A	p.Pro111His	missense	Exon 4 of 7	ENSP00000618017.1

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

GnomAD2 exomes

AF:

0.351

AC:

86468

AN:

246424

AF XY:

0.358

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 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

African (AFR)

AF:

0.271

AC:

9068

AN:

33478

American (AMR)

AF:

0.224

AC:

10027

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.269

AC:

7027

AN:

26128

East Asian (EAS)

AF:

0.222

AC:

8790

AN:

39684

South Asian (SAS)

AF:

0.376

AC:

32431

AN:

86240

European-Finnish (FIN)

AF:

0.515

AC:

27196

AN:

52856

Middle Eastern (MID)

AF:

0.246

AC:

1420

AN:

5766

European-Non Finnish (NFE)

AF:

0.409

AC:

455101

AN:

1111814

Other (OTH)

AF:

0.373

AC:

22540

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

19653

39307

58960

78614

98267

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13936

27872

41808

55744

69680

<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:

0.357

AC:

54298

AN:

151992

Hom.:

10258

Cov.:

AF XY:

0.360

AC XY:

26770

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.280

AC:

11626

AN:

41452

American (AMR)

AF:

0.305

AC:

4667

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.259

AC:

897

AN:

3470

East Asian (EAS)

AF:

0.206

AC:

1059

AN:

5148

South Asian (SAS)

AF:

0.356

AC:

1718

AN:

4822

European-Finnish (FIN)

AF:

0.529

AC:

5599

AN:

10594

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.407

AC:

27608

AN:

67906

Other (OTH)

AF:

0.325

AC:

685

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1739

3479

5218

6958

8697

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

546

1092

1638

2184

2730

<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:

0.366

Hom.:

32730

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.21

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.57

MetaRNN

Benign

0.0030

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.7

PhyloP100

4.6

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-8.0

REVEL

Benign

0.18

Sift

Benign

0.052

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.37

MPC

0.069

ClinPred

0.11

GERP RS

5.7

Varity_R

0.34

gMVP

0.77

Mutation Taster

=78/22

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