Variant chr1-236540574-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_201544.4(LGALS8):c.356A>G(p.Asn119Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,451,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LGALS8
NM_201544.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.56

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 Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.894

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LGALS8	NM_201544.4 linkuse as main transcript	c.356A>G	p.Asn119Ser	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.356A>G	p.Asn119Ser	missense_variant	5/10	1	NM_201544.4	P1	O00214-1
	ENST00000433131.1 linkuse as main transcript	n.142-128T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1451390

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

721508

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000181

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Sep 29, 2023

The c.356A>G (p.N119S) alteration is located in exon 6 (coding exon 4) of the LGALS8 gene. This alteration results from a A to G substitution at nucleotide position 356, causing the asparagine (N) at amino acid position 119 to be replaced by a serine (S). 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

Benign

0.23

BayesDel_addAF

Benign

-0.064

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

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

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.84

T;.;.;D;.;.;D;.;T;T

M_CAP

Benign

0.015

MetaRNN

Pathogenic

0.89

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

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.5

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

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-4.8

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

REVEL

Uncertain

0.34

Sift

Benign

0.054

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

Sift4G

Uncertain

0.059

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

Polyphen

0.67, 0.98

.;P;P;.;P;D;P;D;.;D

Vest4

0.92, 0.92, 0.92, 0.94, 0.91, 0.94, 0.94

MutPred

0.81

Gain of catalytic residue at N119 (P = 0.0236);Gain of catalytic residue at N119 (P = 0.0236);Gain of catalytic residue at N119 (P = 0.0236);Gain of catalytic residue at N119 (P = 0.0236);Gain of catalytic residue at N119 (P = 0.0236);Gain of catalytic residue at N119 (P = 0.0236);Gain of catalytic residue at N119 (P = 0.0236);Gain of catalytic residue at N119 (P = 0.0236);.;Gain of catalytic residue at N119 (P = 0.0236);

MVP

0.69

MPC

0.13

ClinPred

0.98

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.78

gMVP

0.59

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over