12-94255327-T-C

Position:

• chr12-94255327-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005761.3(PLXNC1):​c.3087+31T>C variant causes a intron change. The variant allele was found at a frequency of 0.821 in 1,397,062 control chromosomes in the GnomAD database, including 473,782 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.78 (46709 hom., cov: 34)
  • Exomes 𝑓: 0.83 (427073 hom.)
• Consequence: PLXNC1 NM_005761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.58

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLXNC1	NM_005761.3	c.3087+31T>C		intron_variant		ENST00000258526.9	NP_005752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLXNC1	ENST00000258526.9	c.3087+31T>C		intron_variant		1	NM_005761.3	ENSP00000258526	P1

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118368 AN: 152120 Hom.: 46694 Cov.: 34

Gnomad AFR AF: 0.659

Gnomad AMI AF: 0.889

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.820

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.772

Gnomad FIN AF: 0.880

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.844

Gnomad OTH AF: 0.782

GnomAD3 exomes AF: 0.796 AC: 198874 AN: 249868 Hom.: 79955 AF XY: 0.801 AC XY: 108257 AN XY: 135102

Gnomad AFR exome AF: 0.660

Gnomad AMR exome AF: 0.747

Gnomad ASJ exome AF: 0.816

Gnomad EAS exome AF: 0.615

Gnomad SAS exome AF: 0.785

Gnomad FIN exome AF: 0.880

Gnomad NFE exome AF: 0.844

Gnomad OTH exome AF: 0.811

GnomAD4 exome AF: 0.826 AC: 1028519 AN: 1244824 Hom.: 427073 Cov.: 17 AF XY: 0.826 AC XY: 520714 AN XY: 630640

Gnomad4 AFR exome AF: 0.655

Gnomad4 AMR exome AF: 0.752

Gnomad4 ASJ exome AF: 0.817

Gnomad4 EAS exome AF: 0.632

Gnomad4 SAS exome AF: 0.787

Gnomad4 FIN exome AF: 0.884

Gnomad4 NFE exome AF: 0.845

Gnomad4 OTH exome AF: 0.808

GnomAD4 genome AF: 0.778 AC: 118427 AN: 152238 Hom.: 46709 Cov.: 34 AF XY: 0.777 AC XY: 57842 AN XY: 74450

Gnomad4 AFR AF: 0.659

Gnomad4 AMR AF: 0.776

Gnomad4 ASJ AF: 0.820

Gnomad4 EAS AF: 0.617

Gnomad4 SAS AF: 0.772

Gnomad4 FIN AF: 0.880

Gnomad4 NFE AF: 0.844

Gnomad4 OTH AF: 0.777

Alfa AF: 0.827 Hom.: 72632

Bravo AF: 0.763

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	18
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs865569; hg19: chr12-94649103; COSMIC: COSV51575622; COSMIC: COSV51575622;