LYNX1 p.Met42Leu

Variant names:

• chr8-142775623-T-A
• NM_177477.4:c.124A>T
• LYNX1 p.Met42Leu

Your query was ambiguous. Multiple possible variants found:

• chr8-142775623-T-A
• chr8-142775623-T-G
• chr8-142775621-CAT-TAA
• chr8-142775621-CAT-AAG
• chr8-142775621-CAT-GAG
• chr8-142775621-CAT-TAG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_177477.4(LYNX1):​c.124A>T​(p.Met42Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign 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. M42V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: LYNX1 NM_177477.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.562
• Publications: 0 publications found

Genes affected

LYNX1 (HGNC:29604): (Ly6/neurotoxin 1) This gene encodes a GPI-anchored, cell membrane bound member of the Ly6/uPAR (LU) superfamily of proteins containing the unique three-finger LU domain. This protein interacts with nicotinic acetylcholine receptors (nAChRs), and is thought to function as a modulator of nAChR activity to prevent excessive excitation. Alternatively spliced transcript variants have been found for this gene. Read-through transcription between this gene and the neighboring downstream gene (SLURP2) generates naturally-occurring transcripts (LYNX1-SLURP2) that encode a fusion protein comprised of sequence sharing identity with each individual gene product. [provided by RefSeq, Sep 2017]

LYNX1-SLURP2 (HGNC:52291): (LYNX1-SLURP2 readthrough) This locus represents naturally occurring read-through transcription between the neighboring LYNX1 and SLURP2 genes. The readthrough transcript encodes a fusion protein comprised of sequence sharing identity with each individual gene product. The significance of this read-through transcription and the function of the resulting protein product have not yet been determined. [provided by RefSeq, Sep 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11394739).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177477.4. 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
	LYNX1	NM_177477.4	MANE Select	c.124A>T	p.Met42Leu	missense	Exon 3 of 4	NP_803430.1	P0DP58-1
	LYNX1-SLURP2	NM_023946.5		c.124A>T	p.Met42Leu	missense	Exon 3 of 5	NP_076435.1
	LYNX1	NM_001356370.1		c.124A>T	p.Met42Leu	missense	Exon 3 of 4	NP_001343299.1	P0DP58-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYNX1	ENST00000652477.1	MANE Select	c.124A>T	p.Met42Leu	missense	Exon 3 of 4	ENSP00000498325.1	P0DP58-1
	LYNX1-SLURP2	ENST00000615007.4	TSL:1	c.124A>T	p.Met42Leu	missense	Exon 3 of 5	ENSP00000479586.1
	LYNX1	ENST00000621401.4	TSL:1	c.124A>T	p.Met42Leu	missense	Exon 3 of 4	ENSP00000478390.1	P0DP58-1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Benign	0.56
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.56
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.072
Sift	Benign	0.19	T
Sift4G	Benign	0.81	T
PromoterAI		-0.046	Neutral
Varity_R		0.21
gMVP		0.83
Mutation Taster		=98/2	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr8-143857041;