Variant 19-39658549-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000392051.4(LGALS16):c.182G>A(p.Arg61His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000454 in 1,608,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

LGALS16
ENST00000392051.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.78

Variant links:

Genes affected

LGALS16 (HGNC:40039): (galectin 16) Enables lactose binding activity. Involved in positive regulation of T cell apoptotic process. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LGALS16 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=0.02559191).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGALS16	NM_001190441.3 linkuse as main transcript	c.182G>A	p.Arg61His	missense_variant	3/4	ENST00000392051.4	NP_001177370.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGALS16	ENST00000392051.4 linkuse as main transcript	c.182G>A	p.Arg61His	missense_variant	3/4	1	NM_001190441.3	ENSP00000375904	P1
LGALS16	ENST00000594480.1 linkuse as main transcript	c.*54G>A		3_prime_UTR_variant, NMD_transcript_variant	3/4	3		ENSP00000471564

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000287

AC:

AN:

244044

Hom.:

AF XY:

0.0000227

AC XY:

AN XY:

131962

show subpopulations

Gnomad AFR exome

AF:

0.0000631

Gnomad AMR exome

AF:

0.0000589

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000180

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.0000220

AC:

AN:

1456094

Hom.:

Cov.:

AF XY:

0.0000235

AC XY:

AN XY:

724278

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000203

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000200

Gnomad4 NFE exome

AF:

0.00000990

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000269

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.000468

ExAC

AF:

0.0000165

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

Mar 30, 2024

The c.182G>A (p.R61H) alteration is located in exon 3 (coding exon 3) of the LGALS16 gene. This alteration results from a G to A substitution at nucleotide position 182, causing the arginine (R) at amino acid position 61 to be replaced by a histidine (H). 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

0.11

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.0030

DANN

Benign

0.78

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.00057

M_CAP

Benign

0.00076

MetaRNN

Benign

0.026

MetaSVM

Benign

-0.91

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.020

REVEL

Benign

0.016

Sift

Benign

0.54

Sift4G

Benign

0.54

Vest4

0.12

MVP

0.040

MPC

0.032

ClinPred

0.010

GERP RS

-1.7

gMVP

0.34

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