Variant X-37572057-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001170331.2(LANCL3):c.187G>T(p.Gly63Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000967 in 1,181,450 control chromosomes in the GnomAD database, including 1 homozygotes. There are 355 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00055 ( 0 hom., 22 hem., cov: 24)

Exomes 𝑓: 0.0010 ( 1 hom. 333 hem. )

Consequence

LANCL3
NM_001170331.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.54

Variant links:

Genes affected

LANCL3 (HGNC:24767): (LanC like family member 3) Predicted to be involved in carbohydrate metabolic process. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

LANCL3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03602183).

BS2

High Hemizygotes in GnomAd4 at 22 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LANCL3	NM_001170331.2 linkuse as main transcript	c.187G>T	p.Gly63Trp	missense_variant	1/5	ENST00000378619.4
LANCL3	NM_198511.3 linkuse as main transcript	c.187G>T	p.Gly63Trp	missense_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LANCL3	ENST00000378619.4 linkuse as main transcript	c.187G>T	p.Gly63Trp	missense_variant	1/5	1	NM_001170331.2	P1	Q6ZV70-1
LANCL3	ENST00000378621.7 linkuse as main transcript	c.187G>T	p.Gly63Trp	missense_variant	1/6	1			Q6ZV70-2
LANCL3	ENST00000614025.4 linkuse as main transcript	c.187G>T	p.Gly63Trp	missense_variant	1/5	2			Q6ZV70-2

Frequencies

GnomAD3 genomes

AF:

0.000550

AC:

AN:

112736

Hom.:

Cov.:

AF XY:

0.000630

AC XY:

AN XY:

34896

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000370

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000721

Gnomad FIN

AF:

0.00128

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000771

Gnomad OTH

AF:

0.000654

GnomAD3 exomes

AF:

0.000639

AC:

AN:

126701

Hom.:

AF XY:

0.000667

AC XY:

AN XY:

37479

show subpopulations

Gnomad AFR exome

AF:

0.000252

Gnomad AMR exome

AF:

0.000214

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00117

Gnomad FIN exome

AF:

0.00187

Gnomad NFE exome

AF:

0.000763

Gnomad OTH exome

AF:

0.000289

GnomAD4 exome

AF:

0.00101

AC:

1081

AN:

1068661

Hom.:

Cov.:

AF XY:

0.000965

AC XY:

333

AN XY:

345111

show subpopulations

Gnomad4 AFR exome

AF:

0.000116

Gnomad4 AMR exome

AF:

0.000185

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00107

Gnomad4 FIN exome

AF:

0.00132

Gnomad4 NFE exome

AF:

0.00113

Gnomad4 OTH exome

AF:

0.000690

GnomAD4 genome

AF:

0.000550

AC:

AN:

112789

Hom.:

Cov.:

AF XY:

0.000629

AC XY:

AN XY:

34959

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000369

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000723

Gnomad4 FIN

AF:

0.00128

Gnomad4 NFE

AF:

0.000771

Gnomad4 OTH

AF:

0.000646

Alfa

AF:

0.000536

Hom.:

Bravo

AF:

0.000574

ExAC

AF:

0.000409

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

Oct 04, 2022

The c.187G>T (p.G63W) alteration is located in exon 1 (coding exon 1) of the LANCL3 gene. This alteration results from a G to T substitution at nucleotide position 187, causing the glycine (G) at amino acid position 63 to be replaced by a tryptophan (W). 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

Pathogenic

0.56

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.090

.;.;T

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.67

T;.;T

M_CAP

Pathogenic

0.85

MetaRNN

Benign

0.036

T;T;T

MetaSVM

Benign

-0.74

MutationAssessor

Uncertain

2.8

M;M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.90

PROVEAN

Uncertain

-3.6

.;D;D

REVEL

Benign

0.19

Sift

Uncertain

0.019

.;D;D

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

0.025

B;B;D

Vest4

0.15

MVP

0.30

MPC

1.5

ClinPred

0.094

GERP RS

2.3

Varity_R

0.16

gMVP

0.60

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