rs865569

Variant names:

• chr12-94255327-T-C
• rs865569
• NM_005761.3:c.3087+31T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-94255327-T-C
• chr12-94255327-T-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005761.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLXNC1	NM_005761.3	MANE Select	c.3087+31T>C		intron	N/A	NP_005752.1	O60486

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLXNC1	ENST00000258526.9	TSL:1 MANE Select	c.3087+31T>C		intron	N/A	ENSP00000258526.4	O60486
	PLXNC1	ENST00000549217.5	TSL:1	n.210+31T>C		intron	N/A	ENSP00000446781.1	F8W1K6
	PLXNC1	ENST00000547057.5	TSL:2	c.228+31T>C		intron	N/A	ENSP00000446720.1	B4DHQ7

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

GnomAD2 exomes AF: 0.796 AC: 198874 AN: 249868 AF XY: 0.801

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 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

African (AFR) AF: 0.655 AC: 19187 AN: 29284

American (AMR) AF: 0.752 AC: 33439 AN: 44446

Ashkenazi Jewish (ASJ) AF: 0.817 AC: 20275 AN: 24820

East Asian (EAS) AF: 0.632 AC: 24443 AN: 38686

South Asian (SAS) AF: 0.787 AC: 64462 AN: 81864

European-Finnish (FIN) AF: 0.884 AC: 47068 AN: 53234

Middle Eastern (MID) AF: 0.802 AC: 4313 AN: 5376

European-Non Finnish (NFE) AF: 0.845 AC: 772457 AN: 914052

Other (OTH) AF: 0.808 AC: 42875 AN: 53062

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

African (AFR) AF: 0.659 AC: 27355 AN: 41502

American (AMR) AF: 0.776 AC: 11873 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.820 AC: 2845 AN: 3470

East Asian (EAS) AF: 0.617 AC: 3194 AN: 5180

South Asian (SAS) AF: 0.772 AC: 3728 AN: 4830

European-Finnish (FIN) AF: 0.880 AC: 9334 AN: 10610

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.844 AC: 57423 AN: 68026

Other (OTH) AF: 0.777 AC: 1641 AN: 2112

Alfa AF: 0.819 Hom.: 97532

Bravo AF: 0.763

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	18
DANN	Benign	0.77
PhyloP100		4.6
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs865569; hg19: chr12-94649103; COSMIC: COSV51575622; COSMIC: COSV51575622;