rs146747324

chr12-94279523-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.71

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]

CEP83 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 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_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 95 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLXNC1	NM_005761.3	c.3649T>C	p.Cys1217Arg	missense_variant	22/31	ENST00000258526.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLXNC1	ENST00000258526.9	c.3649T>C	p.Cys1217Arg	missense_variant	22/31	1	NM_005761.3	P1

Frequencies

GnomAD3 genomes AF: 0.000624 AC: 95 AN: 152248 Hom.: 0 Cov.: 33

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.: 0 AF XY: 0.000596 AC XY: 81 AN XY: 135874

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.: 2 Cov.: 32 AF XY: 0.000598 AC XY: 435 AN XY: 727218

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: 95 AN: 152366 Hom.: 0 Cov.: 33 AF XY: 0.000510 AC XY: 38 AN XY: 74522

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.: 0

Bravo AF: 0.000465

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00105 AC: 9

ExAC AF: 0.000610 AC: 74

EpiCase AF: 0.000654

EpiControl AF: 0.00119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Anophthalmia-microphthalmia syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Paul Sabatier University EA-4555, Paul Sabatier University

Jan 01, 2013

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Uncertain	-0.080
Cadd	Uncertain	25
Dann	Uncertain	0.98
DEOGEN2	Benign	0.091	T;T
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.024	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.79	T
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	T
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

Other links and lift over

dbSNP: rs146747324; hg19: chr12-94673299; COSMIC: COSV51573677; COSMIC: COSV51573677;