NM_016341.4:c.*166G>C

Variant names:

• chr10-94328109-G-C
• rs11187870
• NM_016341.4:c.*166G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016341.4(PLCE1):​c.*166G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0719 in 397,822 control chromosomes in the GnomAD database, including 1,438 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.066 (467 hom., cov: 33)
  • Exomes 𝑓: 0.075 (971 hom.)
• Consequence: PLCE1 NM_016341.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.53
• Publications: 19 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 10-94328109-G-C is Benign according to our data. Variant chr10-94328109-G-C is described in ClinVar as Benign. ClinVar VariationId is 301737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.186 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.*166G>C		3_prime_UTR	Exon 33 of 33	NP_057425.3
	PLCE1	NM_001288989.2		c.*166G>C		3_prime_UTR	Exon 33 of 33	NP_001275918.1	B7ZM61
	PLCE1	NM_001165979.2		c.*166G>C		3_prime_UTR	Exon 32 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.*166G>C		3_prime_UTR	Exon 33 of 33	ENSP00000360431.2	Q9P212-1
	PLCE1	ENST00000371375.2	TSL:1	c.*3029G>C		3_prime_UTR	Exon 31 of 31	ENSP00000360426.1	Q9P212-2
	PLCE1	ENST00000875452.1		c.*166G>C		3_prime_UTR	Exon 34 of 34	ENSP00000545511.1

Frequencies

GnomAD3 genomes AF: 0.0666 AC: 10128 AN: 152162 Hom.: 468 Cov.: 33

Gnomad AFR AF: 0.0167

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0751

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.0445

Gnomad FIN AF: 0.0314

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0856

Gnomad OTH AF: 0.0850

GnomAD4 exome AF: 0.0753 AC: 18486 AN: 245540 Hom.: 971 Cov.: 0 AF XY: 0.0742 AC XY: 10281 AN XY: 138526

African (AFR) AF: 0.0179 AC: 120 AN: 6718

American (AMR) AF: 0.0598 AC: 1186 AN: 19846

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 1228 AN: 6592

East Asian (EAS) AF: 0.191 AC: 1694 AN: 8848

South Asian (SAS) AF: 0.0405 AC: 1824 AN: 45076

European-Finnish (FIN) AF: 0.0362 AC: 866 AN: 23916

Middle Eastern (MID) AF: 0.145 AC: 315 AN: 2178

European-Non Finnish (NFE) AF: 0.0844 AC: 10242 AN: 121406

Other (OTH) AF: 0.0922 AC: 1011 AN: 10960

GnomAD4 genome AF: 0.0665 AC: 10124 AN: 152282 Hom.: 467 Cov.: 33 AF XY: 0.0632 AC XY: 4709 AN XY: 74452

African (AFR) AF: 0.0167 AC: 694 AN: 41572

American (AMR) AF: 0.0750 AC: 1147 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 659 AN: 3466

East Asian (EAS) AF: 0.196 AC: 1013 AN: 5176

South Asian (SAS) AF: 0.0444 AC: 214 AN: 4824

European-Finnish (FIN) AF: 0.0314 AC: 333 AN: 10612

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.0856 AC: 5820 AN: 68020

Other (OTH) AF: 0.0841 AC: 178 AN: 2116

Alfa AF: 0.0731 Hom.: 68

Bravo AF: 0.0690

Asia WGS AF: 0.122 AC: 422 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Focal segmental glomerulosclerosis (1)
-	-	1	Nephrotic syndrome, type 3 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	13
DANN	Benign	0.79
PhyloP100		1.5
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: rs11187870; hg19: chr10-96087866;