2-210437710-T-C

Variant summary

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

The NM_006055.3(LANCL1):ā€‹c.853A>Gā€‹(p.Met285Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000492 in 1,604,960 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 32)
Exomes š‘“: 0.000053 ( 0 hom. )

Consequence

LANCL1
NM_006055.3 missense

Scores

3
7
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.67
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-AS1 (HGNC:50727): (LANCL1 antisense RNA 1)

Genome browser will be placed here

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 Protein UniProt
LANCL1NM_006055.3 linkuse as main transcriptc.853A>G p.Met285Val missense_variant 7/10 ENST00000450366.7 NP_006046.1
LANCL1-AS1NR_110604.1 linkuse as main transcriptn.211-4832T>C intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LANCL1ENST00000450366.7 linkuse as main transcriptc.853A>G p.Met285Val missense_variant 7/101 NM_006055.3 ENSP00000393597 P1
LANCL1-AS1ENST00000420418.5 linkuse as main transcriptn.157-4832T>C intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152146
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000938
AC:
23
AN:
245234
Hom.:
0
AF XY:
0.000128
AC XY:
17
AN XY:
132554
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:
0.000780
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000530
AC:
77
AN:
1452814
Hom.:
0
Cov.:
30
AF XY:
0.0000733
AC XY:
53
AN XY:
722568
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:
0.000840
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000451
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152146
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74316
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000890
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.0000988
AC:
12

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 submitterclinical testingAmbry GeneticsMay 23, 2023The c.853A>G (p.M285V) alteration is located in exon 7 (coding exon 6) of the LANCL1 gene. This alteration results from a A to G substitution at nucleotide position 853, causing the methionine (M) at amino acid position 285 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
0.23
BayesDel_addAF
Benign
-0.045
T
BayesDel_noAF
Uncertain
0.080
CADD
Uncertain
25
DANN
Uncertain
0.98
DEOGEN2
Benign
0.19
T;T;T;T;T
Eigen
Pathogenic
0.74
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.75
.;.;.;.;T
M_CAP
Benign
0.056
D
MetaRNN
Uncertain
0.62
D;D;D;D;D
MetaSVM
Benign
-0.55
T
MutationAssessor
Uncertain
2.5
M;M;M;M;M
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.66
T
PROVEAN
Uncertain
-2.7
D;D;D;D;D
REVEL
Uncertain
0.41
Sift
Benign
0.037
D;D;D;D;D
Sift4G
Benign
0.12
T;T;T;T;T
Polyphen
1.0
D;D;D;D;D
Vest4
0.82
MutPred
0.71
Loss of phosphorylation at Y284 (P = 0.3146);Loss of phosphorylation at Y284 (P = 0.3146);Loss of phosphorylation at Y284 (P = 0.3146);Loss of phosphorylation at Y284 (P = 0.3146);Loss of phosphorylation at Y284 (P = 0.3146);
MVP
0.45
MPC
0.046
ClinPred
0.33
T
GERP RS
5.9
Varity_R
0.64
gMVP
0.69

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.

Other links and lift over

dbSNP: rs768489232; hg19: chr2-211302434; API