Variant 12-94149467-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005761.3(PLXNC1):c.496G>A(p.Val166Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0013 in 1,494,764 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00064 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 2 hom. )

Consequence

PLXNC1
NM_005761.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.06

Variant links:

Genes affected

PLXNC1 (HGNC:9106): (plexin C1) This gene encodes a member of the plexin family. Plexins are transmembrane receptors for semaphorins, a large family of proteins that regulate axon guidance, cell motility and migration, and the immune response. The encoded protein and its ligand regulate melanocyte adhesion, and viral semaphorins may modulate the immune response by binding to this receptor. The encoded protein may be a tumor suppressor protein for melanoma. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Jan 2011]

PLXNC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019836694).

BS2

High AC in GnomAd4 at 97 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLXNC1	NM_005761.3 linkuse as main transcript	c.496G>A	p.Val166Met	missense_variant	1/31	ENST00000258526.9	NP_005752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLXNC1	ENST00000258526.9 linkuse as main transcript	c.496G>A	p.Val166Met	missense_variant	1/31	1	NM_005761.3	ENSP00000258526	P1

Frequencies

GnomAD3 genomes

AF:

0.000637

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00124

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000892

AC:

AN:

94190

Hom.:

AF XY:

0.000799

AC XY:

AN XY:

51318

show subpopulations

Gnomad AFR exome

AF:

0.000454

Gnomad AMR exome

AF:

0.000364

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:

0.00201

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

AF:

0.00138

AC:

1850

AN:

1342606

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

890

AN XY:

659676

show subpopulations

Gnomad4 AFR exome

AF:

0.000205

Gnomad4 AMR exome

AF:

0.000399

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000217

Gnomad4 NFE exome

AF:

0.00168

Gnomad4 OTH exome

AF:

0.000768

GnomAD4 genome

AF:

0.000637

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.000538

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00124

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000813

Hom.:

Bravo

AF:

0.000680

ExAC

AF:

0.000447

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

Aug 09, 2021

The c.496G>A (p.V166M) alteration is located in exon 1 (coding exon 1) of the PLXNC1 gene. This alteration results from a G to A substitution at nucleotide position 496, causing the valine (V) at amino acid position 166 to be replaced by a methionine (M). 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

Uncertain

0.43

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.56

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.048

Eigen

Benign

0.034

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.85

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.020

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

MutationTaster

Benign

0.83

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.86

REVEL

Benign

0.020

Sift

Benign

0.080

Sift4G

Benign

0.11

Polyphen

0.27

Vest4

0.46

MVP

0.13

MPC

2.4

ClinPred

0.0080

GERP RS

4.7

Varity_R

0.23

gMVP

0.59

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