Variant rs146747324 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_005761.3(PLXNC1):c.3649T>C(p.Cys1217Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000607 in 1,614,208 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.00062 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00061 ( 2 hom. )

Consequence

PLXNC1
NM_005761.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.71

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:

CEP83 (HGNC:):

CEP83 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02389419).

BP6

Variant 12-94279523-T-C is Benign according to our data. Variant chr12-94279523-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 221924.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 95 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLXNC1	NM_005761.3 linkuse as main transcript	c.3649T>C	p.Cys1217Arg	missense_variant	22/31	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.3649T>C	p.Cys1217Arg	missense_variant	22/31	1	NM_005761.3	ENSP00000258526	P1

Frequencies

GnomAD3 genomes

AF:

0.000624

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00119

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000565

AC:

142

AN:

251420

Hom.:

AF XY:

0.000596

AC XY:

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.000693

Gnomad NFE exome

AF:

0.000976

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000605

AC:

885

AN:

1461842

Hom.:

Cov.:

AF XY:

0.000598

AC XY:

435

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.000917

Gnomad4 NFE exome

AF:

0.000683

Gnomad4 OTH exome

AF:

0.000464

GnomAD4 genome

AF:

0.000623

AC:

AN:

152366

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

AN XY:

74522

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00119

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000901

Hom.:

Bravo

AF:

0.000465

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000610

AC:

EpiCase

AF:

0.000654

EpiControl

AF:

0.00119

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Anophthalmia-microphthalmia syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Paul Sabatier University EA-4555, Paul Sabatier University

Jan 01, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.091

T;T

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.74

T;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.024

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

N;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.79

PROVEAN

Uncertain

-3.2

D;D

REVEL

Benign

0.24

Sift

Uncertain

0.0040

D;T

Sift4G

Uncertain

0.031

D;D

Polyphen

1.0

D;B

Vest4

0.57

MVP

0.53

MPC

2.5

ClinPred

0.060

GERP RS

5.3

Varity_R

0.63

gMVP

0.54

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