rs367640320

Variant names:

• chr10-94252402-C-T
• rs367640320
• NM_016341.4:c.3183C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-94252402-C-T
• chr10-94252402-C-A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_016341.4(PLCE1):​c.3183C>T​(p.Pro1061Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000818 in 1,613,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000082 (0 hom.)
• Consequence: PLCE1 NM_016341.4 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: -1.20
• Publications: 1 publications found

Genes affected

PLCE1 (HGNC:17175): (phospholipase C epsilon 1) This gene encodes a phospholipase enzyme that catalyzes the hydrolysis of phosphatidylinositol-4,5-bisphosphate to generate two second messengers: inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG). These second messengers subsequently regulate various processes affecting cell growth, differentiation, and gene expression. This enzyme is regulated by small monomeric GTPases of the Ras and Rho families and by heterotrimeric G proteins. In addition to its phospholipase C catalytic activity, this enzyme has an N-terminal domain with guanine nucleotide exchange (GEF) activity. Mutations in this gene cause early-onset nephrotic syndrome; characterized by proteinuria, edema, and diffuse mesangial sclerosis or focal and segmental glomerulosclerosis. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Sep 2009]

PLCE1 Gene-Disease associations (from GenCC):

• nephrotic syndrome, type 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, ClinGen, G2P, Labcorp Genetics (formerly Invitae)
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 10-94252402-C-T is Benign according to our data. Variant chr10-94252402-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 301711.
• BP7: Synonymous conserved (PhyloP=-1.2 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016341.4. 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
	PLCE1	NM_016341.4	MANE Select	c.3183C>T	p.Pro1061Pro	synonymous	Exon 9 of 33	NP_057425.3
	PLCE1	NM_001288989.2		c.3183C>T	p.Pro1061Pro	synonymous	Exon 9 of 33	NP_001275918.1	B7ZM61
	PLCE1	NM_001165979.2		c.2259C>T	p.Pro753Pro	synonymous	Exon 8 of 32	NP_001159451.1	Q9P212-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCE1	ENST00000371380.8	TSL:1 MANE Select	c.3183C>T	p.Pro1061Pro	synonymous	Exon 9 of 33	ENSP00000360431.2	Q9P212-1
	PLCE1	ENST00000371375.2	TSL:1	c.2259C>T	p.Pro753Pro	synonymous	Exon 8 of 31	ENSP00000360426.1	Q9P212-2
	PLCE1	ENST00000875452.1		c.3183C>T	p.Pro1061Pro	synonymous	Exon 10 of 34	ENSP00000545511.1

Frequencies

GnomAD3 genomes AF: 0.0000790 AC: 12 AN: 151984 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000112 AC: 28 AN: 249318 AF XY: 0.000104

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000696

Gnomad EAS exome AF: 0.000724

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000619

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000821 AC: 120 AN: 1461812 Hom.: 0 Cov.: 31 AF XY: 0.0000798 AC XY: 58 AN XY: 727208

African (AFR) AF: 0.000149 AC: 5 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00103 AC: 27 AN: 26136

East Asian (EAS) AF: 0.000378 AC: 15 AN: 39688

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5762

European-Non Finnish (NFE) AF: 0.0000549 AC: 61 AN: 1111956

Other (OTH) AF: 0.000116 AC: 7 AN: 60396

GnomAD4 genome AF: 0.0000789 AC: 12 AN: 152102 Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5 AN XY: 74352

African (AFR) AF: 0.0000482 AC: 2 AN: 41486

American (AMR) AF: 0.0000655 AC: 1 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3470

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.000225 Hom.: 0

Bravo AF: 0.000110

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	1	-	Nephrotic syndrome, type 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	2.4
DANN	Benign	0.61
PhyloP100		-1.2
Mutation Taster		=99/1	polymorphism

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: rs367640320; hg19: chr10-96012159; COSMIC: COSV53357365;