rs10507031

Variant names:

• chr12-94199216-T-C
• rs10507031
• NM_005761.3:c.1440-10374T>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.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
• Publications: 6 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=-0.85).
• 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 rank	MANE	Protein	UniProt
PLXNC1	NM_005761.3	c.1440-10374T>C		intron_variant	Intron 4 of 30	ENST00000258526.9	NP_005752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLXNC1	ENST00000258526.9	c.1440-10374T>C		intron_variant	Intron 4 of 30	1	NM_005761.3	ENSP00000258526.4
PLXNC1	ENST00000551850.1	c.288-10374T>C		intron_variant	Intron 4 of 4	4		ENSP00000447843.1

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

African (AFR) AF: 0.198 AC: 8229 AN: 41494

American (AMR) AF: 0.414 AC: 6334 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1725 AN: 3472

East Asian (EAS) AF: 0.585 AC: 3019 AN: 5164

South Asian (SAS) AF: 0.545 AC: 2625 AN: 4816

European-Finnish (FIN) AF: 0.435 AC: 4592 AN: 10566

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.444 AC: 30199 AN: 67964

Other (OTH) AF: 0.409 AC: 864 AN: 2114

Alfa AF: 0.437 Hom.: 8492

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
PhyloP100		0.51
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: rs10507031; hg19: chr12-94592992;