2-210455117-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006055.3(LANCL1):ā€‹c.397T>Cā€‹(p.Cys133Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,613,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.000023 ( 0 hom. )

Consequence

LANCL1
NM_006055.3 missense

Scores

3
8
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.57
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.34367388).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LANCL1NM_006055.3 linkuse as main transcriptc.397T>C p.Cys133Arg missense_variant 4/10 ENST00000450366.7 NP_006046.1
LANCL1-AS1NR_110604.1 linkuse as main transcriptn.369-5358A>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.397T>C p.Cys133Arg missense_variant 4/101 NM_006055.3 ENSP00000393597 P1
LANCL1-AS1ENST00000420418.5 linkuse as main transcriptn.315-5358A>G intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152212
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00116
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000998
AC:
25
AN:
250510
Hom.:
0
AF XY:
0.0000960
AC XY:
13
AN XY:
135358
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00125
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.0000226
AC:
33
AN:
1460874
Hom.:
0
Cov.:
35
AF XY:
0.0000206
AC XY:
15
AN XY:
726764
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000554
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.000133
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152212
Hom.:
0
Cov.:
32
AF XY:
0.000108
AC XY:
8
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.0000965
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00116
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000416
ExAC
AF:
0.0000989
AC:
12
Asia WGS
AF:
0.000289
AC:
1
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 submitterclinical testingAmbry GeneticsOct 12, 2021The c.397T>C (p.C133R) alteration is located in exon 4 (coding exon 3) of the LANCL1 gene. This alteration results from a T to C substitution at nucleotide position 397, causing the cysteine (C) at amino acid position 133 to be replaced by an arginine (R). 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
0.92
BayesDel_addAF
Benign
-0.052
T
BayesDel_noAF
Uncertain
0.11
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Benign
0.18
T;T;T;T;T;T
Eigen
Uncertain
0.66
Eigen_PC
Uncertain
0.59
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Benign
0.85
.;.;.;.;T;T
M_CAP
Benign
0.080
D
MetaRNN
Benign
0.34
T;T;T;T;T;T
MetaSVM
Benign
-0.52
T
MutationAssessor
Uncertain
2.5
M;M;M;M;M;.
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.68
T
PROVEAN
Pathogenic
-8.2
D;D;D;D;D;D
REVEL
Uncertain
0.48
Sift
Uncertain
0.0030
D;D;D;D;D;D
Sift4G
Benign
0.14
T;T;T;T;T;.
Polyphen
0.95
P;P;P;P;P;.
Vest4
0.96
MutPred
0.59
Gain of disorder (P = 0.0057);Gain of disorder (P = 0.0057);Gain of disorder (P = 0.0057);Gain of disorder (P = 0.0057);Gain of disorder (P = 0.0057);Gain of disorder (P = 0.0057);
MVP
0.46
MPC
0.028
ClinPred
0.36
T
GERP RS
5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.96
gMVP
0.79

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: rs775480507; hg19: chr2-211319841; API