Variant chrX-37655794-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_001170331.2(LANCL3):c.680A>G(p.Tyr227Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000125 in 1,203,976 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.000013 ( 0 hom. 1 hem. )

Consequence

LANCL3
NM_001170331.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.73

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 Uncertain_significance. Variant got 2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.891

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LANCL3	NM_001170331.2 linkuse as main transcript	c.680A>G	p.Tyr227Cys	missense_variant	2/5	ENST00000378619.4
LANCL3	NM_198511.3 linkuse as main transcript	c.680A>G	p.Tyr227Cys	missense_variant	2/6
LANCL3	XM_011543904.3 linkuse as main transcript	c.134A>G	p.Tyr45Cys	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LANCL3	ENST00000378619.4 linkuse as main transcript	c.680A>G	p.Tyr227Cys	missense_variant	2/5	1	NM_001170331.2	P1	Q6ZV70-1
LANCL3	ENST00000378621.7 linkuse as main transcript	c.680A>G	p.Tyr227Cys	missense_variant	2/6	1			Q6ZV70-2
LANCL3	ENST00000614025.4 linkuse as main transcript	c.680A>G	p.Tyr227Cys	missense_variant	2/5	2			Q6ZV70-2

Frequencies

GnomAD3 genomes

AF:

0.00000895

AC:

AN:

111748

Hom.:

Cov.:

AF XY:

0.0000295

AC XY:

AN XY:

33892

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

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

179296

Hom.:

AF XY:

0.0000156

AC XY:

AN XY:

64104

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:

0.00

Gnomad NFE exome

AF:

0.0000620

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000128

AC:

AN:

1092228

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

358062

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:

0.0000167

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000895

AC:

AN:

111748

Hom.:

Cov.:

AF XY:

0.0000295

AC XY:

AN XY:

33892

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:

0.0000340

ExAC

AF:

0.0000494

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

Jan 23, 2023

The c.680A>G (p.Y227C) alteration is located in exon 2 (coding exon 2) of the LANCL3 gene. This alteration results from a A to G substitution at nucleotide position 680, causing the tyrosine (Y) at amino acid position 227 to be replaced by a cysteine (C). 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

0.80

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

.;.;T

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

D;.;D

M_CAP

Benign

0.085

MetaRNN

Pathogenic

0.89

D;D;D

MetaSVM

Benign

-0.60

MutationAssessor

Uncertain

2.7

M;M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.88

PROVEAN

Pathogenic

-6.3

.;D;D

REVEL

Uncertain

0.56

Sift

Uncertain

0.0030

.;D;D

Sift4G

Uncertain

0.020

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.85

MutPred

0.77

Loss of catalytic residue at L222 (P = 0.0856);Loss of catalytic residue at L222 (P = 0.0856);Loss of catalytic residue at L222 (P = 0.0856);

MVP

0.92

MPC

1.5

ClinPred

0.80

GERP RS

5.3

Varity_R

0.62

gMVP

0.74

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