chr2-210441399-A-G

Variant summary

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

The NM_006055.3(LANCL1):ā€‹c.452T>Cā€‹(p.Met151Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000589 in 1,611,824 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000033 ( 0 hom., cov: 32)
Exomes š‘“: 0.000062 ( 0 hom. )

Consequence

LANCL1
NM_006055.3 missense

Scores

2
9
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.63
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.452T>C p.Met151Thr missense_variant 5/10 ENST00000450366.7 NP_006046.1
LANCL1-AS1NR_110604.1 linkuse as main transcriptn.211-1143A>G 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.452T>C p.Met151Thr missense_variant 5/101 NM_006055.3 ENSP00000393597 P1
LANCL1-AS1ENST00000420418.5 linkuse as main transcriptn.157-1143A>G intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152206
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:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250940
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135626
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:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000617
AC:
90
AN:
1459618
Hom.:
0
Cov.:
30
AF XY:
0.0000496
AC XY:
36
AN XY:
726114
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
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:
0.0000774
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152206
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74356
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:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000658
Hom.:
0
Bravo
AF:
0.0000378
ExAC
AF:
0.00000824
AC:
1

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 GeneticsJun 16, 2023The c.452T>C (p.M151T) alteration is located in exon 5 (coding exon 4) of the LANCL1 gene. This alteration results from a T to C substitution at nucleotide position 452, causing the methionine (M) at amino acid position 151 to be replaced by a threonine (T). 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
0.71
BayesDel_addAF
Benign
0.0044
T
BayesDel_noAF
Benign
-0.23
CADD
Uncertain
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.17
T;T;T;T;T;T
Eigen
Benign
0.17
Eigen_PC
Uncertain
0.29
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.89
.;.;.;.;D;D
M_CAP
Benign
0.025
T
MetaRNN
Uncertain
0.44
T;T;T;T;T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
2.0
M;M;M;M;M;.
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.63
T
PROVEAN
Uncertain
-2.7
D;D;D;D;D;D
REVEL
Uncertain
0.30
Sift
Uncertain
0.0010
D;D;D;D;D;D
Sift4G
Uncertain
0.0020
D;D;D;D;D;.
Polyphen
0.14
B;B;B;B;B;.
Vest4
0.75
MVP
0.37
MPC
0.011
ClinPred
0.98
D
GERP RS
5.1
Varity_R
0.79
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: rs774622009; hg19: chr2-211306123; API