NM_016341.4:c.810T>C

Variant names:

• chr10-94031856-T-C
• rs17109671
• NM_016341.4:c.810T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_016341.4(PLCE1):​c.810T>C​(p.Cys270Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 1,613,324 control chromosomes in the GnomAD database, including 79,954 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (15101 hom., cov: 32)
  • Exomes 𝑓: 0.29 (64853 hom.)
• Consequence: PLCE1 NM_016341.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.211
• Publications: 23 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: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 10-94031856-T-C is Benign according to our data. Variant chr10-94031856-T-C is described in ClinVar as Benign. ClinVar VariationId is 260733.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.211 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

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.810T>C	p.Cys270Cys	synonymous	Exon 2 of 33	NP_057425.3
	PLCE1	NM_001288989.2		c.810T>C	p.Cys270Cys	synonymous	Exon 2 of 33	NP_001275918.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCE1	ENST00000371380.8	TSL:1 MANE Select	c.810T>C	p.Cys270Cys	synonymous	Exon 2 of 33	ENSP00000360431.2
	PLCE1	ENST00000875452.1		c.810T>C	p.Cys270Cys	synonymous	Exon 3 of 34	ENSP00000545511.1
	PLCE1	ENST00000875451.1		c.810T>C	p.Cys270Cys	synonymous	Exon 2 of 33	ENSP00000545510.1

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60817 AN: 151852 Hom.: 15063 Cov.: 32

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.361

GnomAD2 exomes AF: 0.310 AC: 77151 AN: 248700 AF XY: 0.307

Gnomad AFR exome AF: 0.716

Gnomad AMR exome AF: 0.202

Gnomad ASJ exome AF: 0.303

Gnomad EAS exome AF: 0.465

Gnomad FIN exome AF: 0.293

Gnomad NFE exome AF: 0.266

Gnomad OTH exome AF: 0.275

GnomAD4 exome AF: 0.285 AC: 416776 AN: 1461352 Hom.: 64853 Cov.: 36 AF XY: 0.285 AC XY: 207126 AN XY: 726968

African (AFR) AF: 0.727 AC: 24314 AN: 33456

American (AMR) AF: 0.211 AC: 9447 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 7904 AN: 26120

East Asian (EAS) AF: 0.499 AC: 19810 AN: 39680

South Asian (SAS) AF: 0.317 AC: 27300 AN: 86240

European-Finnish (FIN) AF: 0.287 AC: 15333 AN: 53404

Middle Eastern (MID) AF: 0.274 AC: 1583 AN: 5768

European-Non Finnish (NFE) AF: 0.263 AC: 292202 AN: 1111606

Other (OTH) AF: 0.313 AC: 18883 AN: 60376

GnomAD4 genome AF: 0.401 AC: 60902 AN: 151972 Hom.: 15101 Cov.: 32 AF XY: 0.399 AC XY: 29650 AN XY: 74272

African (AFR) AF: 0.708 AC: 29363 AN: 41460

American (AMR) AF: 0.279 AC: 4256 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1012 AN: 3472

East Asian (EAS) AF: 0.476 AC: 2456 AN: 5156

South Asian (SAS) AF: 0.326 AC: 1572 AN: 4816

European-Finnish (FIN) AF: 0.306 AC: 3235 AN: 10556

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17952 AN: 67948

Other (OTH) AF: 0.360 AC: 760 AN: 2110

Alfa AF: 0.326 Hom.: 6884

Bravo AF: 0.414

Asia WGS AF: 0.398 AC: 1385 AN: 3478

EpiCase AF: 0.278

EpiControl AF: 0.272

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	3	Nephrotic syndrome, type 3 (3)
-	-	3	not specified (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.7
DANN	Benign	0.41
PhyloP100		0.21
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: rs17109671; hg19: chr10-95791613; COSMIC: COSV53354951;