Variant 19-38802026-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006149.4(LGALS4):c.791C>A(p.Thr264Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000626 in 1,614,242 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

LGALS4
NM_006149.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.538

Variant links:

Genes affected

LGALS4 (HGNC:6565): (galectin 4) The galectins are a family of beta-galactoside-binding proteins implicated in modulating cell-cell and cell-matrix interactions. The expression of this gene is restricted to small intestine, colon, and rectum, and it is underexpressed in colorectal cancer. [provided by RefSeq, Jul 2008]

LGALS4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.018226624).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGALS4	NM_006149.4 linkuse as main transcript	c.791C>A	p.Thr264Asn	missense_variant	9/10	ENST00000307751.9	NP_006140.1
LGALS4	XM_011526973.3 linkuse as main transcript	c.752C>A	p.Thr251Asn	missense_variant	8/9		XP_011525275.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
LGALS4	ENST00000307751.9 linkuse as main transcript	c.791C>A	p.Thr264Asn	missense_variant	9/10	1	NM_006149.4	ENSP00000302100	P1
LGALS4	ENST00000600070.1 linkuse as main transcript	c.476C>A	p.Thr159Asn	missense_variant	6/7	3		ENSP00000470387
LGALS4	ENST00000595342.1 linkuse as main transcript	n.351C>A		non_coding_transcript_exon_variant	3/4	3
LGALS4	ENST00000595291.5 linkuse as main transcript	c.*300C>A		3_prime_UTR_variant, NMD_transcript_variant	4/5	5		ENSP00000471757

Frequencies

GnomAD3 genomes

AF:

0.000342

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD3 exomes

AF:

0.0000795

AC:

AN:

251452

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000322

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00122

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000354

AC:

AN:

152352

Hom.:

Cov.:

AF XY:

0.000362

AC XY:

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.00130

Gnomad4 AMR

AF:

0.00

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:

0.00

Alfa

AF:

0.0000575

Hom.:

Bravo

AF:

0.000332

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000107

AC:

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

Aug 26, 2022

The c.791C>A (p.T264N) alteration is located in exon 9 (coding exon 9) of the LGALS4 gene. This alteration results from a C to A substitution at nucleotide position 791, causing the threonine (T) at amino acid position 264 to be replaced by an asparagine (N). 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

0.075

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.76

CADD

Benign

9.8

DANN

Benign

0.84

DEOGEN2

Benign

0.12

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.11

M_CAP

Benign

0.011

MetaRNN

Benign

0.018

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.95

MutationTaster

Benign

1.0

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.2

REVEL

Benign

0.085

Sift

Benign

0.044

Sift4G

Benign

0.15

Polyphen

0.0040

Vest4

0.17

MVP

0.23

MPC

0.14

ClinPred

0.039

GERP RS

3.8

Varity_R

0.35

gMVP

0.40

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