Genetic Variant LGALS8:p.Asp190Gly (chr1-236542934-A-G) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1

The NM_006499.5(LGALS8):c.569A>G(p.Asp190Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00505 in 1,614,106 control chromosomes in the GnomAD database, including 332 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 169 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 163 hom. )

Consequence

LGALS8
NM_006499.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.26

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:

ENSG00000230325 (HGNC:):

ENSG00000230325 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

PM1

In a mutagenesis_site Does not affect localization to cytoplasmic vesicles in case of infection by S.typhimurium. (size 0) in uniprot entity LEG8_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.0021482408).

BP6

Variant 1-236542934-A-G is Benign according to our data. Variant chr1-236542934-A-G is described in ClinVar as [Benign]. Clinvar id is 773294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGALS8	NM_201544.4 link	c.549+147A>G		intron_variant	Intron 7 of 9	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.549+147A>G		intron_variant	Intron 7 of 9	1	NM_201544.4	ENSP00000355543.4		O00214-1

Frequencies

GnomAD3 genomes

AF:

0.0259

AC:

3946

AN:

152128

Hom.:

166

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0893

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0109

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.0177

GnomAD3 exomes

AF:

0.00682

AC:

1715

AN:

251478

Hom.:

AF XY:

0.00479

AC XY:

651

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.0900

Gnomad AMR exome

AF:

0.00489

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000475

Gnomad OTH exome

AF:

0.00375

GnomAD4 exome

AF:

0.00286

AC:

4186

AN:

1461860

Hom.:

163

Cov.:

AF XY:

0.00247

AC XY:

1795

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0926

Gnomad4 AMR exome

AF:

0.00572

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000285

Gnomad4 OTH exome

AF:

0.00714

GnomAD4 genome

AF:

0.0261

AC:

3967

AN:

152246

Hom.:

169

Cov.:

AF XY:

0.0252

AC XY:

1879

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0896

Gnomad4 AMR

AF:

0.0109

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000500

Gnomad4 OTH

AF:

0.0175

Alfa

AF:

0.00470

Hom.:

Bravo

AF:

0.0297

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0876

AC:

386

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00836

AC:

1015

Asia WGS

AF:

0.00664

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0068

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

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.092

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.48

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

MetaRNN

Benign

0.0021

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

MetaSVM

Benign

-0.90

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.43

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

REVEL

Benign

0.073

Sift

Benign

0.13

T;T;D;T;T;T;T

Sift4G

Benign

0.44

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

Polyphen

0.88

P;P;.;P;B;P;B

Vest4

0.39

MVP

0.44

MPC

0.082

ClinPred

0.014

GERP RS

4.1

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over