12-94199216-T-C

Position:

• chr12-94199216-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.1440-10374T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 152,090 control chromosomes in the GnomAD database, including 12,333 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 0.38 (12333 hom., cov: 32)
• Consequence: PLXNC1 NM_005761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.508

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLXNC1	NM_005761.3	c.1440-10374T>C		intron_variant		ENST00000258526.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLXNC1	ENST00000258526.9	c.1440-10374T>C		intron_variant		1	NM_005761.3	P1
PLXNC1	ENST00000551850.1	c.288-10374T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58256 AN: 151972 Hom.: 12331 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.383 AC: 58257 AN: 152090 Hom.: 12333 Cov.: 32 AF XY: 0.388 AC XY: 28806 AN XY: 74328

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.414

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.585

Gnomad4 SAS AF: 0.545

Gnomad4 FIN AF: 0.435

Gnomad4 NFE AF: 0.444

Gnomad4 OTH AF: 0.409

Alfa AF: 0.438 Hom.: 7759

Bravo AF: 0.374

Asia WGS AF: 0.521 AC: 1809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.4
DANN	Benign	0.66

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: rs10507031; hg19: chr12-94592992;