2-210437692-T-C

Position:

• chr2-210437692-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006055.3(LANCL1):​c.871A>G​(p.Lys291Glu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000007 in 1,428,232 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: LANCL1 NM_006055.3 missense, splice_region
• Scores: Splicing: ADA: 0.03955
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.72

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)

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.801

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LANCL1	NM_006055.3	c.871A>G	p.Lys291Glu	missense_variant, splice_region_variant	7/10	ENST00000450366.7	NP_006046.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LANCL1	ENST00000450366.7	c.871A>G	p.Lys291Glu	missense_variant, splice_region_variant	7/10	1	NM_006055.3	ENSP00000393597.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1428232 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 709942

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 9.10e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2023

The c.871A>G (p.K291E) alteration is located in exon 7 (coding exon 6) of the LANCL1 gene. This alteration results from a A to G substitution at nucleotide position 871, causing the lysine (K) at amino acid position 291 to be replaced by a glutamic acid (E). 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	0.15
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.042	T;T;T;T;T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	.;.;.;.;D
M_CAP	Benign	0.022	T
MetaRNN	Pathogenic	0.80	D;D;D;D;D
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.8	L;L;L;L;L
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.6	N;N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.19	T;T;T;T;T
Sift4G	Benign	0.32	T;T;T;T;T
Polyphen		0.94	P;P;P;P;P
Vest4		0.85
MutPred		0.51		Loss of methylation at K291 (P = 0.0122);Loss of methylation at K291 (P = 0.0122);Loss of methylation at K291 (P = 0.0122);Loss of methylation at K291 (P = 0.0122);Loss of methylation at K291 (P = 0.0122);
MVP		0.47
MPC		0.033
ClinPred		0.88	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.43
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.040
dbscSNV1_RF	Benign	0.27
SpliceAI score (max)		0.030		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: chr2-211302416;