chr2-210436331-T-C

Variant summary

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

The NM_006055.3(LANCL1):ā€‹c.935A>Gā€‹(p.Tyr312Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000212 in 1,613,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000059 ( 0 hom., cov: 31)
Exomes š‘“: 0.00023 ( 0 hom. )

Consequence

LANCL1
NM_006055.3 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.466
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16275221).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LANCL1NM_006055.3 linkuse as main transcriptc.935A>G p.Tyr312Cys missense_variant 8/10 ENST00000450366.7 NP_006046.1
LANCL1-AS1NR_110604.1 linkuse as main transcriptn.211-6211T>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.935A>G p.Tyr312Cys missense_variant 8/101 NM_006055.3 ENSP00000393597 P1
LANCL1-AS1ENST00000420418.5 linkuse as main transcriptn.157-6211T>C intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.0000592
AC:
9
AN:
152118
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000483
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:
0.000103
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000876
AC:
22
AN:
251192
Hom.:
0
AF XY:
0.0000737
AC XY:
10
AN XY:
135734
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.0000289
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:
0.000159
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.000228
AC:
333
AN:
1461814
Hom.:
0
Cov.:
30
AF XY:
0.000224
AC XY:
163
AN XY:
727206
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000289
Gnomad4 OTH exome
AF:
0.000149
GnomAD4 genome
AF:
0.0000592
AC:
9
AN:
152118
Hom.:
0
Cov.:
31
AF XY:
0.0000807
AC XY:
6
AN XY:
74318
show subpopulations
Gnomad4 AFR
AF:
0.0000483
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:
0.000103
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000182
Hom.:
0
Bravo
AF:
0.000121
TwinsUK
AF:
0.00108
AC:
4
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000465
AC:
4
ExAC
AF:
0.0000824
AC:
10
EpiCase
AF:
0.000273
EpiControl
AF:
0.000237

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 GeneticsFeb 16, 2023The c.935A>G (p.Y312C) 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 935, causing the tyrosine (Y) at amino acid position 312 to be replaced by a cysteine (C). 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
0.085
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
20
DANN
Benign
0.94
DEOGEN2
Benign
0.31
T;T;T;T;T
Eigen
Benign
-0.48
Eigen_PC
Benign
-0.46
FATHMM_MKL
Benign
0.13
N
LIST_S2
Benign
0.86
.;.;.;.;D
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.16
T;T;T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
1.0
L;L;L;L;L
MutationTaster
Benign
1.0
N;N;N;N;N
PrimateAI
Benign
0.28
T
PROVEAN
Uncertain
-2.5
D;D;D;D;D
REVEL
Benign
0.056
Sift
Uncertain
0.019
D;D;D;D;D
Sift4G
Uncertain
0.0070
D;D;D;D;D
Polyphen
0.035
B;B;B;B;B
Vest4
0.37
MVP
0.27
MPC
0.0080
ClinPred
0.028
T
GERP RS
3.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.27
gMVP
0.48

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: rs143380318; hg19: chr2-211301055; COSMIC: COSV52067468; COSMIC: COSV52067468; API