1-236540609-G-A

Position:

chr1-236540609-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_201544.4(LGALS8):c.391G>A(p.Gly131Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,610,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

LGALS8
NM_201544.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0940

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.027314812).

BP6

Variant 1-236540609-G-A is Benign according to our data. Variant chr1-236540609-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2296707.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LGALS8	NM_201544.4 linkuse as main transcript	c.391G>A	p.Gly131Ser	missense_variant	5/10	ENST00000366584.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LGALS8	ENST00000366584.9 linkuse as main transcript	c.391G>A	p.Gly131Ser	missense_variant	5/10	1	NM_201544.4	P1	O00214-1
	ENST00000433131.1 linkuse as main transcript	n.142-163C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

151888

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000960

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

248004

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134070

show subpopulations

Gnomad AFR exome

AF:

0.0000622

Gnomad AMR exome

AF:

0.0000300

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000891

AC:

AN:

1458330

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

725374

show subpopulations

Gnomad4 AFR exome

AF:

0.0000600

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000395

AC:

AN:

151888

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74158

show subpopulations

Gnomad4 AFR

AF:

0.0000484

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000960

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 24, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

5.3

DANN

Benign

0.56

DEOGEN2

Benign

0.0017

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

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.76

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

M_CAP

Benign

0.0037

MetaRNN

Benign

0.027

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

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.3

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

MutationTaster

Benign

1.0

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

PrimateAI

Benign

0.22

PROVEAN

Benign

0.91

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

REVEL

Benign

0.024

Sift

Benign

0.53

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

Sift4G

Benign

0.73

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

Polyphen

0.0

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

Vest4

0.13, 0.12, 0.10, 0.13, 0.11, 0.14

MutPred

0.46

Gain of phosphorylation at G131 (P = 0.0684);Gain of phosphorylation at G131 (P = 0.0684);Gain of phosphorylation at G131 (P = 0.0684);Gain of phosphorylation at G131 (P = 0.0684);Gain of phosphorylation at G131 (P = 0.0684);Gain of phosphorylation at G131 (P = 0.0684);Gain of phosphorylation at G131 (P = 0.0684);Gain of phosphorylation at G131 (P = 0.0684);.;Gain of phosphorylation at G131 (P = 0.0684);

MVP

0.17

MPC

0.053

ClinPred

0.010

GERP RS

0.47

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.078

gMVP

0.32

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