rs770292132

Variant names:

• chr8-142775674-C-A
• NM_177477.4:c.73G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-142775674-C-A
• chr8-142775674-C-G
• chr8-142775674-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43

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

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=0.25133094).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYNX1	NM_177477.4	c.73G>T	p.Val25Leu	missense_variant	Exon 3 of 4	ENST00000652477.1	NP_803430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LYNX1	ENST00000652477.1	c.73G>T	p.Val25Leu	missense_variant	Exon 3 of 4		NM_177477.4	ENSP00000498325.1
LYNX1-SLURP2	ENST00000615007.4	c.73G>T	p.Val25Leu	missense_variant	Exon 3 of 5	1		ENSP00000479586.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1448296 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 719000

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: 9.04e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T;.;.;.;.;.;.
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.80	T;T;T;.;.;T;T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.25	T;T;T;T;T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.69	.;.;N;N;N;.;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-2.7	D;.;.;.;.;.;.
REVEL	Benign	0.24
Sift	Pathogenic	0.0	D;.;.;.;.;.;.
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D
Vest4		0.64
MutPred		0.25		Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);
MVP		0.15
ClinPred		0.75	D
GERP RS		3.9
Varity_R		0.20
gMVP		0.91

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-143857092;