Genetic Variant NM_177477.4:c.73G>T (chr8-142775674-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_177477.4(LYNX1):c.73G>T(p.Val25Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,448,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. V25M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

LYNX1
NM_177477.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.43

Publications

0 publications found

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 links:

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]

LYNX1-SLURP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.25133094).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LYNX1	NM_177477.4	MANE Select	c.73G>T	p.Val25Leu	missense	Exon 3 of 4	NP_803430.1	P0DP58-1
LYNX1-SLURP2	NM_023946.5		c.73G>T	p.Val25Leu	missense	Exon 3 of 5	NP_076435.1
LYNX1	NM_001356370.1		c.73G>T	p.Val25Leu	missense	Exon 3 of 4	NP_001343299.1	P0DP58-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LYNX1	ENST00000652477.1	MANE Select	c.73G>T	p.Val25Leu	missense	Exon 3 of 4	ENSP00000498325.1	P0DP58-1
LYNX1-SLURP2	ENST00000615007.4	TSL:1	c.73G>T	p.Val25Leu	missense	Exon 3 of 5	ENSP00000479586.1
LYNX1	ENST00000621401.4	TSL:1	c.73G>T	p.Val25Leu	missense	Exon 3 of 4	ENSP00000478390.1	P0DP58-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.90e-7

AC:

AN:

1448296

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719000

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33258

American (AMR)

AF:

0.00

AC:

AN:

42564

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25866

East Asian (EAS)

AF:

0.00

AC:

AN:

39176

South Asian (SAS)

AF:

0.00

AC:

AN:

83728

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52340

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

9.04e-7

AC:

AN:

1105696

Other (OTH)

AF:

0.00

AC:

AN:

59910

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.80

M_CAP

Benign

0.031

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.69

PhyloP100

1.4

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.24

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.64

MutPred

0.25

Loss of sheet (P = 0.0126)

MVP

0.15

ClinPred

0.75

GERP RS

3.9

PromoterAI

0.087

Neutral

(source)

Varity_R

0.20

gMVP

0.91

Mutation Taster

=99/1

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over