rs3203713

Variant names:

• chr10-94327971-A-G
• rs3203713
• NM_016341.4:c.*28A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-94327971-A-G
• chr10-94327971-A-T

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.*28A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 531,220 control chromosomes in the GnomAD database, including 6,423 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1594 hom., cov: 33)
  • Exomes 𝑓: 0.15 (4829 hom.)
• Consequence: PLCE1 NM_016341.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.11
• Publications: 14 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 (REVEL=0.011).
• BP6: Variant 10-94327971-A-G is Benign according to our data. Variant chr10-94327971-A-G is described in ClinVar as Benign. ClinVar VariationId is 301735.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.164 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.*28A>G		3_prime_UTR	Exon 33 of 33	NP_057425.3
	PLCE1	NM_001288989.2		c.*28A>G		3_prime_UTR	Exon 33 of 33	NP_001275918.1	B7ZM61
	PLCE1	NM_001165979.2		c.*28A>G		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.*28A>G		3_prime_UTR	Exon 33 of 33	ENSP00000360431.2	Q9P212-1
	PLCE1	ENST00000371375.2	TSL:1	c.*2891A>G		3_prime_UTR	Exon 31 of 31	ENSP00000360426.1	Q9P212-2
	PLCE1	ENST00000875452.1		c.*28A>G		3_prime_UTR	Exon 34 of 34	ENSP00000545511.1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20962 AN: 152068 Hom.: 1594 Cov.: 33

Gnomad AFR AF: 0.0982

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.00211

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.155

GnomAD2 exomes AF: 0.135 AC: 32566 AN: 241530 AF XY: 0.141

Gnomad AFR exome AF: 0.0956

Gnomad AMR exome AF: 0.0750

Gnomad ASJ exome AF: 0.205

Gnomad EAS exome AF: 0.00169

Gnomad FIN exome AF: 0.158

Gnomad NFE exome AF: 0.160

Gnomad OTH exome AF: 0.156

GnomAD4 exome AF: 0.149 AC: 56548 AN: 379034 Hom.: 4829 Cov.: 0 AF XY: 0.154 AC XY: 33248 AN XY: 215846

African (AFR) AF: 0.0981 AC: 1028 AN: 10484

American (AMR) AF: 0.0765 AC: 2765 AN: 36144

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 2405 AN: 11624

East Asian (EAS) AF: 0.00175 AC: 23 AN: 13174

South Asian (SAS) AF: 0.166 AC: 10974 AN: 66256

European-Finnish (FIN) AF: 0.158 AC: 4908 AN: 31068

Middle Eastern (MID) AF: 0.221 AC: 627 AN: 2842

European-Non Finnish (NFE) AF: 0.164 AC: 31224 AN: 190854

Other (OTH) AF: 0.156 AC: 2594 AN: 16588

GnomAD4 genome AF: 0.138 AC: 20958 AN: 152186 Hom.: 1594 Cov.: 33 AF XY: 0.137 AC XY: 10227 AN XY: 74408

African (AFR) AF: 0.0980 AC: 4069 AN: 41508

American (AMR) AF: 0.116 AC: 1775 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 752 AN: 3470

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5190

South Asian (SAS) AF: 0.163 AC: 783 AN: 4814

European-Finnish (FIN) AF: 0.151 AC: 1602 AN: 10594

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11356 AN: 67992

Other (OTH) AF: 0.155 AC: 328 AN: 2116

Alfa AF: 0.158 Hom.: 1369

Bravo AF: 0.129

Asia WGS AF: 0.0890 AC: 309 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	14
DANN	Uncertain	0.98
PhyloP100		2.1
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: rs3203713; hg19: chr10-96087728;