10-94030532-TA-T

Variant names:

• chr10-94030532-TA-T
• rs59044005
• NM_016341.4:c.-364-141delA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_016341.4(PLCE1):​c.-364-141delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0214 in 147,502 control chromosomes in the GnomAD database, including 126 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.021 (126 hom., cov: 32)
• Consequence: PLCE1 NM_016341.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.646
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 10-94030532-TA-T is Benign according to our data. Variant chr10-94030532-TA-T is described in ClinVar as [Benign]. Clinvar id is 1260323.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCE1	NM_016341.4	c.-364-141delA		intron_variant	Intron 1 of 32	ENST00000371380.8	NP_057425.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCE1	ENST00000371380.8	c.-364-150delA		intron_variant	Intron 1 of 32	1	NM_016341.4	ENSP00000360431.2

Frequencies

GnomAD3 genomes AF: 0.0214 AC: 3155 AN: 147416 Hom.: 125 Cov.: 32

Gnomad AFR AF: 0.0717

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0124

Gnomad ASJ AF: 0.000587

Gnomad EAS AF: 0.000592

Gnomad SAS AF: 0.000641

Gnomad FIN AF: 0.000527

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000466

Gnomad OTH AF: 0.0198

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0214 AC: 3163 AN: 147502 Hom.: 126 Cov.: 32 AF XY: 0.0212 AC XY: 1524 AN XY: 71780

African (AFR) AF: 0.0717 AC: 2896 AN: 40386

American (AMR) AF: 0.0124 AC: 183 AN: 14740

Ashkenazi Jewish (ASJ) AF: 0.000587 AC: 2 AN: 3410

East Asian (EAS) AF: 0.000594 AC: 3 AN: 5052

South Asian (SAS) AF: 0.000643 AC: 3 AN: 4664

European-Finnish (FIN) AF: 0.000527 AC: 5 AN: 9492

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.000466 AC: 31 AN: 66536

Other (OTH) AF: 0.0196 AC: 40 AN: 2036

Alfa AF: 0.000500 Hom.: 0

Bravo AF: 0.0250

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 07, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.65
Mutation Taster		=100/0	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: rs59044005; hg19: chr10-95790289;