Genetic Variant LGALS8:p.Met56Val (chr1-236538910-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_201544.4(LGALS8):c.166A>G(p.Met56Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 1,611,126 control chromosomes in the GnomAD database, including 408,385 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.70 ( 37413 hom., cov: 32)

Exomes 𝑓: 0.71 ( 370972 hom. )

Consequence

LGALS8
NM_201544.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.115

Variant links:

Genes affected

LGALS8 (HGNC:6569): (galectin 8) This gene encodes a member of the galectin family. Galectins are beta-galactoside-binding animal lectins with conserved carbohydrate recognition domains. The galectins have been implicated in many essential functions including development, differentiation, cell-cell adhesion, cell-matrix interaction, growth regulation, apoptosis, and RNA splicing. This gene is widely expressed in tumoral tissues and seems to be involved in integrin-like cell interactions. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

LGALS8 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=7.61474E-7).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGALS8	NM_201544.4 link	c.166A>G	p.Met56Val	missense_variant	Exon 4 of 10	ENST00000366584.9	NP_963838.1	O00214-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LGALS8	ENST00000366584.9 link	c.166A>G	p.Met56Val	missense_variant	Exon 4 of 10	1	NM_201544.4	ENSP00000355543.4		O00214-1

Frequencies

GnomAD3 genomes

AF:

0.700

AC:

106202

AN:

151764

Hom.:

37404

Cov.:

show subpopulations

Gnomad AFR

AF:

0.686

Gnomad AMI

AF:

0.653

Gnomad AMR

AF:

0.674

Gnomad ASJ

AF:

0.683

Gnomad EAS

AF:

0.633

Gnomad SAS

AF:

0.529

Gnomad FIN

AF:

0.764

Gnomad MID

AF:

0.697

Gnomad NFE

AF:

0.723

Gnomad OTH

AF:

0.708

GnomAD3 exomes

AF:

0.678

AC:

170168

AN:

250880

Hom.:

58372

AF XY:

0.672

AC XY:

91152

AN XY:

135594

show subpopulations

Gnomad AFR exome

AF:

0.682

Gnomad AMR exome

AF:

0.647

Gnomad ASJ exome

AF:

0.674

Gnomad EAS exome

AF:

0.633

Gnomad SAS exome

AF:

0.539

Gnomad FIN exome

AF:

0.747

Gnomad NFE exome

AF:

0.719

Gnomad OTH exome

AF:

0.692

GnomAD4 exome

AF:

0.710

AC:

1036725

AN:

1459246

Hom.:

370972

Cov.:

AF XY:

0.705

AC XY:

511732

AN XY:

726070

show subpopulations

Gnomad4 AFR exome

AF:

0.685

Gnomad4 AMR exome

AF:

0.650

Gnomad4 ASJ exome

AF:

0.674

Gnomad4 EAS exome

AF:

0.614

Gnomad4 SAS exome

AF:

0.544

Gnomad4 FIN exome

AF:

0.751

Gnomad4 NFE exome

AF:

0.730

Gnomad4 OTH exome

AF:

0.698

GnomAD4 genome

AF:

0.700

AC:

106264

AN:

151880

Hom.:

37413

Cov.:

AF XY:

0.697

AC XY:

51702

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.685

Gnomad4 AMR

AF:

0.674

Gnomad4 ASJ

AF:

0.683

Gnomad4 EAS

AF:

0.633

Gnomad4 SAS

AF:

0.529

Gnomad4 FIN

AF:

0.764

Gnomad4 NFE

AF:

0.723

Gnomad4 OTH

AF:

0.708

Alfa

AF:

0.711

Hom.:

55477

Bravo

AF:

0.692

ESP6500AA

AF:

0.680

AC:

2995

ESP6500EA

AF:

0.707

AC:

6077

ExAC

AF:

0.676

AC:

82040

Asia WGS

AF:

0.594

AC:

2067

AN:

3478

EpiCase

AF:

0.710

EpiControl

AF:

0.703

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.045

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

6.2

DANN

Benign

0.70

DEOGEN2

Benign

0.00091

.;.;.;T;.;T;.;T;T;.;T;.;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.091

LIST_S2

Benign

0.12

T;T;.;T;.;T;.;.;T;T;.;T;T;.

MetaRNN

Benign

7.6e-7

T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.5

.;.;N;.;N;.;N;N;.;N;N;.;N;.

PrimateAI

Benign

0.31

PROVEAN

Benign

0.93

N;N;N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.029

Sift

Benign

1.0

T;T;T;T;T;T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.43

T;T;T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.0

.;.;B;.;B;.;B;B;B;B;B;.;B;B

Vest4

0.015, 0.038, 0.016, 0.037, 0.045, 0.017, 0.024, 0.040, 0.030

MPC

0.054

ClinPred

0.0013

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.072

gMVP

0.19

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