Variant 19-2291206-C-T 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_001101391.3(LINGO3):c.571G>A(p.Gly191Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000617 in 1,457,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

LINGO3
NM_001101391.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.61

Variant links:

Genes affected

LINGO3 (HGNC:21206): (leucine rich repeat and Ig domain containing 3) Predicted to be integral component of membrane. Predicted to be active in extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

LINGO3 links:

ENSG00000273734 (HGNC:):

ENSG00000273734 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=0.1670655).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LINGO3	NM_001101391.3 linkuse as main transcript	c.571G>A	p.Gly191Arg	missense_variant	2/2	ENST00000698372.1	NP_001094861.1	P0C6S8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LINGO3	ENST00000698372.1 linkuse as main transcript	c.571G>A	p.Gly191Arg	missense_variant	2/2		NM_001101391.3	ENSP00000513689.1	P0C6S8
ENSG00000273734	ENST00000621615.1 linkuse as main transcript	n.146+21462C>T		intron_variant		2		ENSP00000481965.1	A0A087WYN8
LINGO3	ENST00000585527.1 linkuse as main transcript	c.571G>A	p.Gly191Arg	missense_variant	1/1	6		ENSP00000467753.2	P0C6S8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000128

AC:

AN:

234494

Hom.:

AF XY:

0.00000775

AC XY:

AN XY:

129084

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000591

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000572

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:

0.00000617

AC:

AN:

1457608

Hom.:

Cov.:

AF XY:

0.00000690

AC XY:

AN XY:

724940

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000451

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000167

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

Oct 26, 2022

The c.571G>A (p.G191R) alteration is located in exon 2 (coding exon 1) of the LINGO3 gene. This alteration results from a G to A substitution at nucleotide position 571, causing the glycine (G) at amino acid position 191 to be replaced by an arginine (R). 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

0.28

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0050

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.31

LIST_S2

Uncertain

0.87

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.0

PrimateAI

Pathogenic

0.80

Sift4G

Benign

0.13

Polyphen

0.80

Vest4

0.26

MutPred

0.37

Loss of catalytic residue at G191 (P = 0.0152);

MVP

0.37

ClinPred

0.31

GERP RS

3.4

Varity_R

0.092

gMVP

0.67

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.

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