Genetic Variant LANCL3:p.Ala26Val (chrX-37571947-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001170331.2(LANCL3):c.77C>T(p.Ala26Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000415 in 1,203,681 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000027 ( 0 hom. 0 hem. )

Consequence

LANCL3
NM_001170331.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.69

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19179127).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LANCL3	NM_001170331.2 link	c.77C>T	p.Ala26Val	missense_variant	Exon 1 of 5	ENST00000378619.4	NP_001163802.1	Q6ZV70-1
LANCL3	NM_198511.3 link	c.77C>T	p.Ala26Val	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.77C>T	p.Ala26Val	missense_variant	Exon 1 of 5	1	NM_001170331.2	ENSP00000367882.4	Q6ZV70-1
LANCL3	ENST00000378621.7 link	c.77C>T	p.Ala26Val	missense_variant	Exon 1 of 6	1		ENSP00000367885.3	Q6ZV70-2
ENSG00000250349	ENST00000465127.1 link	c.171+145947C>T		intron_variant	Intron 3 of 8	5		ENSP00000417050.1	B4E171
LANCL3	ENST00000614025.4 link	c.77C>T	p.Ala26Val	missense_variant	Exon 1 of 5	2		ENSP00000479231.1	Q6ZV70-2

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112569

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34765

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:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1091112

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

358374

show subpopulations

Gnomad4 AFR exome

AF:

0.0000381

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000238

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000178

AC:

AN:

112569

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34765

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:

0.0000376

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.77C>T (p.A26V) alteration is located in exon 1 (coding exon 1) of the LANCL3 gene. This alteration results from a C to T substitution at nucleotide position 77, causing the alanine (A) at amino acid position 26 to be replaced by a valine (V). 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

0.087

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.017

.;.;T

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.74

T;.;T

M_CAP

Pathogenic

0.72

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;L;L

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.27

.;N;N

REVEL

Benign

0.072

Sift

Benign

0.51

.;T;T

Sift4G

Benign

0.51

T;T;T

Polyphen

0.59

P;P;P

Vest4

0.22

MutPred

0.30

Loss of glycosylation at P29 (P = 0.3215);Loss of glycosylation at P29 (P = 0.3215);Loss of glycosylation at P29 (P = 0.3215);

MVP

0.26

MPC

0.47

ClinPred

0.50

GERP RS

3.9

Varity_R

0.10

gMVP

0.24

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