rs942676

Variant names:

• chr10-94316738-C-G
• rs942676
• NM_016341.4:c.6324C>G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_016341.4(PLCE1):​c.6324C>G​(p.Val2108Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,612,102 control chromosomes in the GnomAD database, including 22,053 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1569 hom., cov: 32)
  • Exomes 𝑓: 0.16 (20484 hom.)
• Consequence: PLCE1 NM_016341.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 2.41
• Publications: 12 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]

NOC3L (HGNC:24034): (NOC3 like DNA replication regulator) Enables RNA binding activity. Predicted to be involved in DNA replication initiation. Predicted to act upstream of or within fat cell differentiation. Located in mitochondrion; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 10-94316738-C-G is Benign according to our data. Variant chr10-94316738-C-G is described in ClinVar as Benign. ClinVar VariationId is 260729.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.41 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.166 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.6324C>G	p.Val2108Val	synonymous	Exon 29 of 33	NP_057425.3
	PLCE1	NM_001288989.2		c.6276C>G	p.Val2092Val	synonymous	Exon 29 of 33	NP_001275918.1
	PLCE1	NM_001165979.2		c.5400C>G	p.Val1800Val	synonymous	Exon 28 of 32	NP_001159451.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCE1	ENST00000371380.8	TSL:1 MANE Select	c.6324C>G	p.Val2108Val	synonymous	Exon 29 of 33	ENSP00000360431.2
	PLCE1	ENST00000371375.2	TSL:1	c.5400C>G	p.Val1800Val	synonymous	Exon 28 of 31	ENSP00000360426.1
	PLCE1	ENST00000875452.1		c.6324C>G	p.Val2108Val	synonymous	Exon 30 of 34	ENSP00000545511.1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18804 AN: 152048 Hom.: 1570 Cov.: 32

Gnomad AFR AF: 0.0300

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.0789

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.105

GnomAD2 exomes AF: 0.146 AC: 36403 AN: 249302 AF XY: 0.147

Gnomad AFR exome AF: 0.0266

Gnomad AMR exome AF: 0.172

Gnomad ASJ exome AF: 0.0767

Gnomad EAS exome AF: 0.000723

Gnomad FIN exome AF: 0.238

Gnomad NFE exome AF: 0.168

Gnomad OTH exome AF: 0.137

GnomAD4 exome AF: 0.160 AC: 233965 AN: 1459936 Hom.: 20484 Cov.: 31 AF XY: 0.160 AC XY: 116043 AN XY: 726396

African (AFR) AF: 0.0225 AC: 753 AN: 33472

American (AMR) AF: 0.171 AC: 7634 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0782 AC: 2043 AN: 26116

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39680

South Asian (SAS) AF: 0.141 AC: 12169 AN: 86220

European-Finnish (FIN) AF: 0.236 AC: 12625 AN: 53392

Middle Eastern (MID) AF: 0.0697 AC: 402 AN: 5764

European-Non Finnish (NFE) AF: 0.171 AC: 189688 AN: 1110242

Other (OTH) AF: 0.143 AC: 8642 AN: 60332

GnomAD4 genome AF: 0.124 AC: 18801 AN: 152166 Hom.: 1569 Cov.: 32 AF XY: 0.125 AC XY: 9310 AN XY: 74360

African (AFR) AF: 0.0299 AC: 1243 AN: 41546

American (AMR) AF: 0.154 AC: 2360 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0789 AC: 274 AN: 3472

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5176

South Asian (SAS) AF: 0.131 AC: 633 AN: 4814

European-Finnish (FIN) AF: 0.231 AC: 2442 AN: 10568

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11471 AN: 67994

Other (OTH) AF: 0.104 AC: 219 AN: 2114

Alfa AF: 0.146 Hom.: 602

Bravo AF: 0.111

Asia WGS AF: 0.0610 AC: 213 AN: 3478

EpiCase AF: 0.154

EpiControl AF: 0.152

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	5.6
DANN	Benign	0.78
PhyloP100		2.4
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs942676; hg19: chr10-96076495;