8-142775631-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_177477.4(LYNX1):​c.116G>A​(p.Cys39Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000437 in 1,602,400 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. C39S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

LYNX1
NM_177477.4 missense

Scores

10
5
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.28
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.873

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LYNX1NM_177477.4 linkc.116G>A p.Cys39Tyr missense_variant Exon 3 of 4 ENST00000652477.1 NP_803430.1 P0DP58-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LYNX1ENST00000652477.1 linkc.116G>A p.Cys39Tyr missense_variant Exon 3 of 4 NM_177477.4 ENSP00000498325.1 P0DP58-1
LYNX1-SLURP2ENST00000615007.4 linkc.116G>A p.Cys39Tyr missense_variant Exon 3 of 5 1 ENSP00000479586.1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152226
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000876
AC:
2
AN:
228228
Hom.:
0
AF XY:
0.00000811
AC XY:
1
AN XY:
123294
show subpopulations
Gnomad AFR exome
AF:
0.000142
Gnomad AMR exome
AF:
0.00
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000414
AC:
6
AN:
1450174
Hom.:
0
Cov.:
34
AF XY:
0.00000278
AC XY:
2
AN XY:
720140
show subpopulations
Gnomad4 AFR exome
AF:
0.000180
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152226
Hom.:
0
Cov.:
34
AF XY:
0.0000134
AC XY:
1
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.00000825
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.97
BayesDel_addAF
Pathogenic
0.39
D
BayesDel_noAF
Pathogenic
0.32
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.27
T;.;.;.;.;.;.
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.78
T;T;T;.;.;T;T
M_CAP
Pathogenic
0.44
D
MetaRNN
Pathogenic
0.87
D;D;D;D;D;D;D
MetaSVM
Uncertain
0.72
D
MutationAssessor
Benign
0.69
.;.;N;N;N;.;.
PrimateAI
Pathogenic
0.79
T
PROVEAN
Pathogenic
-11
D;.;.;.;.;.;.
REVEL
Pathogenic
0.69
Sift
Pathogenic
0.0
D;.;.;.;.;.;.
Sift4G
Pathogenic
0.0
D;D;D;D;D;D;D
Vest4
0.74
MutPred
0.44
Loss of catalytic residue at M37 (P = 0.001);Loss of catalytic residue at M37 (P = 0.001);Loss of catalytic residue at M37 (P = 0.001);Loss of catalytic residue at M37 (P = 0.001);Loss of catalytic residue at M37 (P = 0.001);Loss of catalytic residue at M37 (P = 0.001);Loss of catalytic residue at M37 (P = 0.001);
MVP
0.83
ClinPred
0.98
D
GERP RS
4.8
Varity_R
0.95
gMVP
1.0

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: rs778932411; hg19: chr8-143857049; API