12-94185249-T-C

Variant names:

• chr12-94185249-T-C
• rs3847810
• NM_005761.3:c.1339-1124T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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]

ENSG00000258035 (HGNC:58451):

ACMG classification

Our verdict: Benign. The variant received -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.

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.1339-1124T>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.1339-1124T>C		intron	N/A	ENSP00000258526.4	O60486
	PLXNC1	ENST00000551850.1	TSL:4	c.187-1124T>C		intron	N/A	ENSP00000447843.1	F8VUW4
	ENSG00000258035	ENST00000659763.1		n.2108A>G		non_coding_transcript_exon	Exon 2 of 2

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

African (AFR) AF: 0.200 AC: 8282 AN: 41496

American (AMR) AF: 0.186 AC: 2841 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 635 AN: 3472

East Asian (EAS) AF: 0.285 AC: 1474 AN: 5168

South Asian (SAS) AF: 0.190 AC: 914 AN: 4822

European-Finnish (FIN) AF: 0.173 AC: 1830 AN: 10602

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 13012 AN: 67984

Other (OTH) AF: 0.184 AC: 390 AN: 2114

Alfa AF: 0.194 Hom.: 12280

Bravo AF: 0.195

Asia WGS AF: 0.214 AC: 743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.90
DANN	Benign	0.49
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3847810; hg19: chr12-94579025;