Variant 1-236540671-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_201544.4(LGALS8):c.453T>G(p.Phe151Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,608,972 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 3 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 1 hom. )

Consequence

LGALS8
NM_201544.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.686

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11069074).

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGALS8	NM_201544.4 linkuse as main transcript	c.453T>G	p.Phe151Leu	missense_variant	5/10	ENST00000366584.9	NP_963838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGALS8	ENST00000366584.9 linkuse as main transcript	c.453T>G	p.Phe151Leu	missense_variant	5/10	1	NM_201544.4	ENSP00000355543	P1	O00214-1
	ENST00000433131.1 linkuse as main transcript	n.142-225A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.0000122

AC:

AN:

245994

Hom.:

AF XY:

0.00000753

AC XY:

AN XY:

132840

show subpopulations

Gnomad AFR exome

AF:

0.0000621

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000555

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1456678

Hom.:

Cov.:

AF XY:

0.0000166

AC XY:

AN XY:

724358

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.000151

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000412

AC:

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 06, 2023

The c.453T>G (p.F151L) alteration is located in exon 6 (coding exon 4) of the LGALS8 gene. This alteration results from a T to G substitution at nucleotide position 453, causing the phenylalanine (F) at amino acid position 151 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.29

CADD

Benign

2.9

DANN

Benign

0.90

DEOGEN2

Benign

0.0091

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

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.12

LIST_S2

Uncertain

0.86

D;.;.;D;.;.;D;.;D;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.11

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

MetaSVM

Benign

-0.99

MutationAssessor

Pathogenic

3.4

.;M;M;.;M;M;M;M;.;M

MutationTaster

Benign

0.97

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

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-3.3

D;D;D;D;D;D;D;D;D;D

REVEL

Benign

0.20

Sift

Uncertain

0.0020

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

Sift4G

Uncertain

0.010

D;D;D;D;D;D;D;D;D;D

Polyphen

0.24, 0.10

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

Vest4

0.75, 0.70, 0.75, 0.67, 0.75, 0.72, 0.75, 0.66

MutPred

0.58

Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);.;Loss of sheet (P = 0.0817);

MVP

0.28

MPC

0.19

ClinPred

0.25

GERP RS

-3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.56

gMVP

0.62

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over