chr2-210436259-T-C
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_006055.3(LANCL1):āc.1007A>Gā(p.Tyr336Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000105 in 1,613,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 31)
Exomes š: 0.000011 ( 0 hom. )
Consequence
LANCL1
NM_006055.3 missense
NM_006055.3 missense
Scores
6
10
3
Clinical Significance
Conservation
PhyloP100: 3.96
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.961
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LANCL1 | NM_006055.3 | c.1007A>G | p.Tyr336Cys | missense_variant | 8/10 | ENST00000450366.7 | NP_006046.1 | |
LANCL1-AS1 | NR_110604.1 | n.211-6283T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LANCL1 | ENST00000450366.7 | c.1007A>G | p.Tyr336Cys | missense_variant | 8/10 | 1 | NM_006055.3 | ENSP00000393597 | P1 | |
LANCL1-AS1 | ENST00000420418.5 | n.157-6283T>C | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152028Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251210Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135752
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GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461788Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 8AN XY: 727192
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 152028Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74270
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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 | May 20, 2024 | The c.1007A>G (p.Y336C) 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 1007, causing the tyrosine (Y) at amino acid position 336 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;.;.;.;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
H;H;H;H;H
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;D
Polyphen
D;D;D;D;D
Vest4
MutPred
Gain of helix (P = 0.2684);Gain of helix (P = 0.2684);Gain of helix (P = 0.2684);Gain of helix (P = 0.2684);Gain of helix (P = 0.2684);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at