12-94170142-C-T

Position:

• chr12-94170142-C-T

Variant summary

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

The NM_005761.3(PLXNC1):​c.1203+849C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 152,016 control chromosomes in the GnomAD database, including 31,284 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 0.64 (31284 hom., cov: 32)
• Consequence: PLXNC1 NM_005761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLXNC1	NM_005761.3	c.1203+849C>T		intron_variant		ENST00000258526.9	NP_005752.1
LOC124902988	XR_007063411.1	n.84-1791G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLXNC1	ENST00000258526.9	c.1203+849C>T		intron_variant		1	NM_005761.3	ENSP00000258526	P1
	ENST00000669622.1	n.1105-1791G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97422 AN: 151898 Hom.: 31258 Cov.: 32

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.692

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.641 AC: 97490 AN: 152016 Hom.: 31284 Cov.: 32 AF XY: 0.643 AC XY: 47796 AN XY: 74312

Gnomad4 AFR AF: 0.652

Gnomad4 AMR AF: 0.610

Gnomad4 ASJ AF: 0.607

Gnomad4 EAS AF: 0.693

Gnomad4 SAS AF: 0.712

Gnomad4 FIN AF: 0.653

Gnomad4 NFE AF: 0.633

Gnomad4 OTH AF: 0.627

Alfa AF: 0.632 Hom.: 56979

Bravo AF: 0.637

Asia WGS AF: 0.671 AC: 2331 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	0.34
DANN	Benign	0.51

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: rs2365736; hg19: chr12-94563918;