12-94256549-A-G

Position:

• chr12-94256549-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005761.3(PLXNC1):​c.3087+1253A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 151,676 control chromosomes in the GnomAD database, including 25,603 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 0.58 (25603 hom., cov: 29)
• Consequence: PLXNC1 NM_005761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.357

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLXNC1	NM_005761.3	c.3087+1253A>G		intron_variant		ENST00000258526.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLXNC1	ENST00000258526.9	c.3087+1253A>G		intron_variant		1	NM_005761.3	P1
PLXNC1	ENST00000549217.5	c.210+1253A>G		intron_variant, NMD_transcript_variant		1
PLXNC1	ENST00000547057.5	c.228+1253A>G		intron_variant		2
PLXNC1	ENST00000550080.5	c.228+1253A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87743 AN: 151558 Hom.: 25573 Cov.: 29

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.576

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.579 AC: 87830 AN: 151676 Hom.: 25603 Cov.: 29 AF XY: 0.578 AC XY: 42844 AN XY: 74118

Gnomad4 AFR AF: 0.619

Gnomad4 AMR AF: 0.595

Gnomad4 ASJ AF: 0.523

Gnomad4 EAS AF: 0.523

Gnomad4 SAS AF: 0.542

Gnomad4 FIN AF: 0.593

Gnomad4 NFE AF: 0.559

Gnomad4 OTH AF: 0.574

Alfa AF: 0.561 Hom.: 31423

Bravo AF: 0.581

Asia WGS AF: 0.572 AC: 1989 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.6
DANN	Benign	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: rs2242499; hg19: chr12-94650325;