Genetic Variant LANCL3:p.Lys97Met (chrX-37572160-A-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001170331.2(LANCL3):c.290A>T(p.Lys97Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000387 in 1,189,981 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 23 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000040 ( 0 hom. 23 hem. )

Consequence

LANCL3
NM_001170331.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.40

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:

ENSG00000250349 (HGNC:):

ENSG00000250349 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.30742717).

BS2

High Hemizygotes in GnomAdExome4 at 23 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LANCL3	NM_001170331.2 link	c.290A>T	p.Lys97Met	missense_variant	Exon 1 of 5	ENST00000378619.4	NP_001163802.1	Q6ZV70-1
LANCL3	NM_198511.3 link	c.290A>T	p.Lys97Met	missense_variant	Exon 1 of 6		NP_940913.1	Q6ZV70-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LANCL3	ENST00000378619.4 link	c.290A>T	p.Lys97Met	missense_variant	Exon 1 of 5	1	NM_001170331.2	ENSP00000367882.4	Q6ZV70-1
LANCL3	ENST00000378621.7 link	c.290A>T	p.Lys97Met	missense_variant	Exon 1 of 6	1		ENSP00000367885.3	Q6ZV70-2
ENSG00000250349	ENST00000465127.1 link	c.171+146160A>T		intron_variant	Intron 3 of 8	5		ENSP00000417050.1	B4E171
LANCL3	ENST00000614025.4 link	c.290A>T	p.Lys97Met	missense_variant	Exon 1 of 5	2		ENSP00000479231.1	Q6ZV70-2

Frequencies

GnomAD3 genomes

AF:

0.0000267

AC:

AN:

112266

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34448

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000566

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000268

AC:

AN:

149176

Hom.:

AF XY:

0.0000200

AC XY:

AN XY:

50086

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000799

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000457

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000399

AC:

AN:

1077715

Hom.:

Cov.:

AF XY:

0.0000652

AC XY:

AN XY:

352723

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000134

Gnomad4 SAS exome

AF:

0.000190

Gnomad4 FIN exome

AF:

0.0000337

Gnomad4 NFE exome

AF:

0.0000310

Gnomad4 OTH exome

AF:

0.0000441

GnomAD4 genome

AF:

0.0000267

AC:

AN:

112266

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34448

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:

0.00

Gnomad4 NFE

AF:

0.0000566

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000604

ExAC

AF:

0.00000847

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.290A>T (p.K97M) alteration is located in exon 1 (coding exon 1) of the LANCL3 gene. This alteration results from a A to T substitution at nucleotide position 290, causing the lysine (K) at amino acid position 97 to be replaced by a methionine (M). 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

0.33

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.041

.;.;T

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.55

T;.;T

M_CAP

Pathogenic

0.67

MetaRNN

Benign

0.31

T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

1.7

L;L;L

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-2.0

.;N;N

REVEL

Benign

0.12

Sift

Benign

0.056

.;T;T

Sift4G

Uncertain

0.027

D;D;D

Polyphen

0.96

D;D;B

Vest4

0.22

MutPred

0.55

Loss of MoRF binding (P = 0.0806);Loss of MoRF binding (P = 0.0806);Loss of MoRF binding (P = 0.0806);

MVP

0.18

MPC

0.70

ClinPred

0.11

GERP RS

4.6

Varity_R

0.098

gMVP

0.52

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