Variant 8-142775677-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_177477.4(LYNX1):c.70C>T(p.His24Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000188 in 1,598,898 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LYNX1
NM_177477.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.397

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:):

LYNX1-SLURP2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16318044).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYNX1	NM_177477.4 linkuse as main transcript	c.70C>T	p.His24Tyr	missense_variant	3/4	ENST00000652477.1	NP_803430.1
LYNX1-SLURP2	NM_023946.5 linkuse as main transcript	c.70C>T	p.His24Tyr	missense_variant	3/5		NP_076435.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYNX1	ENST00000652477.1 linkuse as main transcript	c.70C>T	p.His24Tyr	missense_variant	3/4		NM_177477.4	ENSP00000498325	P1	P0DP58-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

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

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1446656

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

718006

show subpopulations

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:

0.00000181

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.00000826

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 05, 2023

The c.70C>T (p.H24Y) alteration is located in exon 3 (coding exon 2) of the LYNX1 gene. This alteration results from a C to T substitution at nucleotide position 70, causing the histidine (H) at amino acid position 24 to be replaced by a tyrosine (Y). 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

0.32

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

T;.;.;.;.;.;.

Eigen

Benign

-0.12

Eigen_PC

Benign

0.0030

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.70

T;T;T;.;.;T;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.16

T;T;T;T;T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

0.69

.;.;N;N;N;.;.

MutationTaster

Benign

0.50

N;N;N;N;N

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-5.1

D;.;.;.;.;.;.

REVEL

Benign

0.071

Sift

Benign

0.11

T;.;.;.;.;.;.

Sift4G

Benign

0.16

T;T;T;T;T;T;T

Vest4

0.50

MutPred

0.45

Gain of solvent accessibility (P = 0.0739);Gain of solvent accessibility (P = 0.0739);Gain of solvent accessibility (P = 0.0739);Gain of solvent accessibility (P = 0.0739);Gain of solvent accessibility (P = 0.0739);Gain of solvent accessibility (P = 0.0739);Gain of solvent accessibility (P = 0.0739);

MVP

0.095

ClinPred

0.32

GERP RS

3.7

Varity_R

0.27

gMVP

0.90

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over