12-94214068-C-T

Variant names:

• chr12-94214068-C-T
• rs7316309
• NM_005761.3:c.1554+4364C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005761.3(PLXNC1):​c.1554+4364C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 148,810 control chromosomes in the GnomAD database, including 3,573 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 (3573 hom., cov: 29)
• Consequence: PLXNC1 NM_005761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127
• Publications: 2 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLXNC1	NM_005761.3	c.1554+4364C>T		intron_variant	Intron 5 of 30	ENST00000258526.9	NP_005752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLXNC1	ENST00000258526.9	c.1554+4364C>T		intron_variant	Intron 5 of 30	1	NM_005761.3	ENSP00000258526.4

Frequencies

GnomAD3 genomes AF: 0.193 AC: 28671 AN: 148690 Hom.: 3560 Cov.: 29

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.0991

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.193 AC: 28705 AN: 148810 Hom.: 3573 Cov.: 29 AF XY: 0.193 AC XY: 13990 AN XY: 72398

African (AFR) AF: 0.350 AC: 14238 AN: 40634

American (AMR) AF: 0.165 AC: 2414 AN: 14632

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 403 AN: 3450

East Asian (EAS) AF: 0.237 AC: 1185 AN: 5006

South Asian (SAS) AF: 0.162 AC: 752 AN: 4630

European-Finnish (FIN) AF: 0.139 AC: 1372 AN: 9878

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 292

European-Non Finnish (NFE) AF: 0.117 AC: 7861 AN: 67358

Other (OTH) AF: 0.175 AC: 358 AN: 2042

Alfa AF: 0.151 Hom.: 357

Bravo AF: 0.199

Asia WGS AF: 0.190 AC: 660 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.5
DANN	Benign	0.78
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7316309; hg19: chr12-94607844;