2-210441399-A-C

Variant names:

• chr2-210441399-A-C
• rs774622009
• NM_006055.3:c.452T>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006055.3(LANCL1):​c.452T>G​(p.Met151Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M151T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LANCL1 NM_006055.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.63
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.905

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006055.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LANCL1	NM_006055.3	MANE Select	c.452T>G	p.Met151Arg	missense	Exon 5 of 10	NP_006046.1	O43813
	LANCL1	NM_001136574.2		c.452T>G	p.Met151Arg	missense	Exon 5 of 10	NP_001130046.1	Q53TN2
	LANCL1	NM_001136575.2		c.452T>G	p.Met151Arg	missense	Exon 5 of 10	NP_001130047.1	Q53TN2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LANCL1	ENST00000450366.7	TSL:1 MANE Select	c.452T>G	p.Met151Arg	missense	Exon 5 of 10	ENSP00000393597.2	O43813
	LANCL1	ENST00000233714.8	TSL:1	c.452T>G	p.Met151Arg	missense	Exon 5 of 10	ENSP00000233714.4	O43813
	LANCL1	ENST00000431941.6	TSL:1	c.452T>G	p.Met151Arg	missense	Exon 5 of 10	ENSP00000397646.2	O43813

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.031	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	2.0	M
PhyloP100		8.6
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.52	P
Vest4		0.90
MutPred		0.90		Gain of disorder (P = 0.0475)
MVP		0.45
MPC		0.017
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.96
gMVP		0.86
Mutation Taster		=45/55	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs774622009; hg19: chr2-211306123;