Variant 2-210436256-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006055.3(LANCL1):c.1010A>G(p.Asn337Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000123 in 1,461,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

LANCL1
NM_006055.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.66

Variant links:

Genes affected

LANCL1 (HGNC:6508): (LanC like glutathione S-transferase 1) This gene encodes a loosely associated peripheral membrane protein related to the LanC family of bacterial membrane-associated proteins involved in the biosynthesis of antimicrobial peptides. This protein may play a role as a peptide-modifying enzyme component in eukaryotic cells. Previously considered a member of the G-protein-coupled receptor superfamily, this protein is now in the LanC family. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Nov 2008]

LANCL1 links:

LANCL1-AS1 (HGNC:50727): (LANCL1 antisense RNA 1)

LANCL1-AS1 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=0.19860879).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LANCL1	NM_006055.3 link	c.1010A>G	p.Asn337Ser	missense_variant	8/10	ENST00000450366.7	NP_006046.1	O43813Q53TN2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LANCL1	ENST00000450366.7 link	c.1010A>G	p.Asn337Ser	missense_variant	8/10	1	NM_006055.3	ENSP00000393597.2		O43813

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1461776

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727188

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:

0.0000162

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Aug 19, 2024

The c.1010A>G (p.N337S) alteration is located in exon 8 (coding exon 7) of the LANCL1 gene. This alteration results from a A to G substitution at nucleotide position 1010, causing the asparagine (N) at amino acid position 337 to be replaced by a serine (S). 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

0.081

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.035

T;T;T;T;T

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.80

.;.;.;.;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.20

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

M;M;M;M;M

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.1

N;N;N;N;N

REVEL

Benign

0.17

Sift

Benign

0.059

T;T;T;T;T

Sift4G

Uncertain

0.040

D;D;D;D;D

Polyphen

0.0020

B;B;B;B;B

Vest4

0.13

MutPred

0.51

Gain of catalytic residue at Y336 (P = 0.2642);Gain of catalytic residue at Y336 (P = 0.2642);Gain of catalytic residue at Y336 (P = 0.2642);Gain of catalytic residue at Y336 (P = 0.2642);Gain of catalytic residue at Y336 (P = 0.2642);

MVP

0.29

MPC

0.0083

ClinPred

0.50

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.080

gMVP

0.16

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over