rs2068435

Variant names:

• chr12-94267198-T-C
• rs2068435
• NM_005761.3:c.3597+1973T>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.3597+1973T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,178 control chromosomes in the GnomAD database, including 1,839 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 0.16 (1839 hom., cov: 33)
• Consequence: PLXNC1 NM_005761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.04
• Publications: 4 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]

CEP83 (HGNC:17966): (centrosomal protein 83) The protein encoded by this gene is a centriolar protein involved in primary cilium assembly. Defects in this gene have been associated with infantile nephronophthisis and intellectual disability. [provided by RefSeq, Oct 2016]

CEP83 Gene-Disease associations (from GenCC):

• nephronophthisis 18

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp, G2P
• nephronophthisis 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.185 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.3597+1973T>C		intron	N/A	NP_005752.1
	PLXNC1	NR_037687.2		n.292+1973T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLXNC1	ENST00000258526.9	TSL:1 MANE Select	c.3597+1973T>C		intron	N/A	ENSP00000258526.4
	PLXNC1	ENST00000545312.1	TSL:1	c.-187+1973T>C		intron	N/A	ENSP00000439225.1
	PLXNC1	ENST00000549217.5	TSL:1	n.720+1973T>C		intron	N/A	ENSP00000446781.1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23735 AN: 152060 Hom.: 1839 Cov.: 33

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.156 AC: 23739 AN: 152178 Hom.: 1839 Cov.: 33 AF XY: 0.155 AC XY: 11524 AN XY: 74380

African (AFR) AF: 0.148 AC: 6164 AN: 41518

American (AMR) AF: 0.191 AC: 2924 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 515 AN: 3470

East Asian (EAS) AF: 0.163 AC: 843 AN: 5174

South Asian (SAS) AF: 0.135 AC: 652 AN: 4822

European-Finnish (FIN) AF: 0.147 AC: 1560 AN: 10592

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10459 AN: 67996

Other (OTH) AF: 0.176 AC: 372 AN: 2110

Alfa AF: 0.155 Hom.: 615

Bravo AF: 0.163

Asia WGS AF: 0.141 AC: 489 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	13
DANN	Benign	0.44
PhyloP100		3.0
Mutation Taster		=98/2	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: rs2068435; hg19: chr12-94660974;