Variant 19-39657929-T-C 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_001190441.3(LGALS16):c.62T>C(p.Ile21Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,224 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Consequence

LGALS16
NM_001190441.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.646

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=0.05264914).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGALS16	NM_001190441.3 linkuse as main transcript	c.62T>C	p.Ile21Thr	missense_variant	2/4	ENST00000392051.4	NP_001177370.2	A8MUM7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGALS16	ENST00000392051.4 linkuse as main transcript	c.62T>C	p.Ile21Thr	missense_variant	2/4	1	NM_001190441.3	ENSP00000375904.2		A8MUM7
LGALS16	ENST00000594480.1 linkuse as main transcript	n.117T>C		non_coding_transcript_exon_variant	2/4	3		ENSP00000471564.1		M0R108

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251312

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

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

Dec 03, 2024

The c.62T>C (p.I21T) alteration is located in exon 2 (coding exon 2) of the LGALS16 gene. This alteration results from a T to C substitution at nucleotide position 62, causing the isoleucine (I) at amino acid position 21 to be replaced by a threonine (T). 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

0.13

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.12

DANN

Benign

0.19

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.00055

M_CAP

Benign

0.00065

MetaRNN

Benign

0.053

MetaSVM

Benign

-0.91

PrimateAI

Benign

0.44

PROVEAN

Benign

0.88

REVEL

Benign

0.019

Sift

Benign

1.0

Sift4G

Benign

0.62

Vest4

0.046

MutPred

0.40

Loss of stability (P = 0.0065);

MVP

0.030

MPC

0.032

ClinPred

0.043

GERP RS

-2.4

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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