Variant X-37571911-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001170331.2(LANCL3):c.41A>T(p.Tyr14Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000746 in 1,206,098 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.0000073 ( 0 hom. 0 hem. )

Consequence

LANCL3
NM_001170331.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.68

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LANCL3	NM_001170331.2 linkuse as main transcript	c.41A>T	p.Tyr14Phe	missense_variant	1/5	ENST00000378619.4
LANCL3	NM_198511.3 linkuse as main transcript	c.41A>T	p.Tyr14Phe	missense_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LANCL3	ENST00000378619.4 linkuse as main transcript	c.41A>T	p.Tyr14Phe	missense_variant	1/5	1	NM_001170331.2	P1	Q6ZV70-1
LANCL3	ENST00000378621.7 linkuse as main transcript	c.41A>T	p.Tyr14Phe	missense_variant	1/6	1			Q6ZV70-2
LANCL3	ENST00000614025.4 linkuse as main transcript	c.41A>T	p.Tyr14Phe	missense_variant	1/5	2			Q6ZV70-2

Frequencies

GnomAD3 genomes

AF:

0.00000889

AC:

AN:

112469

Hom.:

Cov.:

AF XY:

0.0000288

AC XY:

AN XY:

34685

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000732

AC:

AN:

1093629

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

360689

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000951

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000889

AC:

AN:

112469

Hom.:

Cov.:

AF XY:

0.0000288

AC XY:

AN XY:

34685

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:

0.0000188

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 17, 2023

The c.41A>T (p.Y14F) 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 41, causing the tyrosine (Y) at amino acid position 14 to be replaced by a phenylalanine (F). 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

0.15

BayesDel_addAF

Uncertain

0.060

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

.;.;T

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.87

D;.;D

M_CAP

Pathogenic

0.64

MetaRNN

Uncertain

0.59

D;D;D

MetaSVM

Benign

-0.80

MutationAssessor

Benign

1.0

L;L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-1.1

.;N;N

REVEL

Benign

0.21

Sift

Benign

0.37

.;T;T

Sift4G

Benign

0.40

T;T;T

Polyphen

0.97

D;D;D

Vest4

0.45

MutPred

0.69

Loss of phosphorylation at Y14 (P = 0.0716);Loss of phosphorylation at Y14 (P = 0.0716);Loss of phosphorylation at Y14 (P = 0.0716);

MVP

0.57

MPC

0.64

ClinPred

0.75

GERP RS

4.8

Varity_R

0.47

gMVP

0.31

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