12-94185249-T-C

Position:

• chr12-94185249-T-C

Variant summary

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

The NM_005761.3(PLXNC1):​c.1339-1124T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,150 control chromosomes in the GnomAD database, including 2,926 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 0.19 (2926 hom., cov: 32)
• Consequence: PLXNC1 NM_005761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.432

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]

(HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLXNC1	NM_005761.3	c.1339-1124T>C		intron_variant		ENST00000258526.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLXNC1	ENST00000258526.9	c.1339-1124T>C		intron_variant		1	NM_005761.3	P1
	ENST00000669622.1	n.1104+693A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29537 AN: 152032 Hom.: 2905 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.194 AC: 29592 AN: 152150 Hom.: 2926 Cov.: 32 AF XY: 0.194 AC XY: 14415 AN XY: 74392

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.285

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.184

Alfa AF: 0.194 Hom.: 5907

Bravo AF: 0.195

Asia WGS AF: 0.214 AC: 743 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	0.90
DANN	Benign	0.49

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: rs3847810; hg19: chr12-94579025;