2-210440624-C-T

Variant summary

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

The NM_006055.3(LANCL1):​c.664G>A​(p.Ala222Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,368 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

LANCL1
NM_006055.3 missense

Scores

14
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.34
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)

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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.664G>A p.Ala222Thr missense_variant 6/10 ENST00000450366.7 NP_006046.1
LANCL1-AS1NR_110604.1 linkuse as main transcriptn.211-1918C>T 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.664G>A p.Ala222Thr missense_variant 6/101 NM_006055.3 ENSP00000393597 P1
LANCL1-AS1ENST00000420418.5 linkuse as main transcriptn.157-1918C>T intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460368
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
726388
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 GeneticsApr 01, 2024The c.664G>A (p.A222T) alteration is located in exon 6 (coding exon 5) of the LANCL1 gene. This alteration results from a G to A substitution at nucleotide position 664, causing the alanine (A) at amino acid position 222 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
Benign
0.20
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.020
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.19
T;T;T;T;T
Eigen
Uncertain
0.37
Eigen_PC
Uncertain
0.40
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.84
.;.;.;.;T
M_CAP
Benign
0.034
D
MetaRNN
Uncertain
0.60
D;D;D;D;D
MetaSVM
Uncertain
-0.12
T
MutationAssessor
Uncertain
2.7
M;M;M;M;M
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.73
T
PROVEAN
Uncertain
-3.0
D;D;D;D;D
REVEL
Uncertain
0.31
Sift
Uncertain
0.024
D;D;D;D;D
Sift4G
Uncertain
0.023
D;D;D;D;D
Polyphen
0.81
P;P;P;P;P
Vest4
0.61
MutPred
0.61
Loss of stability (P = 0.2535);Loss of stability (P = 0.2535);Loss of stability (P = 0.2535);Loss of stability (P = 0.2535);Loss of stability (P = 0.2535);
MVP
0.48
MPC
0.041
ClinPred
0.98
D
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.63
gMVP
0.67

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-211305348; API