chr10-94325021-AAGG-A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 1P and 9B. PM4_SupportingBP6BS1BS2

The NM_016341.4(PLCE1):​c.6856_6858delGAG​(p.Glu2286del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.00017 in 1,614,162 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00018 ( 2 hom. )

Consequence

PLCE1
NM_016341.4 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: 5.48

Publications

0 publications found
Variant links:
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]

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

PM4
Nonframeshift variant in NON repetitive region in NM_016341.4. Strenght limited to Supporting due to length of the change: 1aa.
BP6
Variant 10-94325021-AAGG-A is Benign according to our data. Variant chr10-94325021-AAGG-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 448044.We mark this variant Likely_benign, oryginal submission is: [Conflicting_classifications_of_pathogenicity].
BS1
Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0000788 (12/152306) while in subpopulation SAS AF = 0.00249 (12/4826). AF 95% confidence interval is 0.00143. There are 0 homozygotes in GnomAd4. There are 8 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
BS2
High Homozygotes in GnomAdExome4 at 2 AR,AD gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PLCE1NM_016341.4 linkc.6856_6858delGAG p.Glu2286del conservative_inframe_deletion Exon 32 of 33 ENST00000371380.8 NP_057425.3 Q9P212-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PLCE1ENST00000371380.8 linkc.6856_6858delGAG p.Glu2286del conservative_inframe_deletion Exon 32 of 33 1 NM_016341.4 ENSP00000360431.2 Q9P212-1

Frequencies

GnomAD3 genomes
AF:
0.0000788
AC:
12
AN:
152188
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00248
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.000393
AC:
98
AN:
249516
AF XY:
0.000532
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000556
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000883
Gnomad OTH exome
AF:
0.000495
GnomAD4 exome
AF:
0.000179
AC:
262
AN:
1461856
Hom.:
2
AF XY:
0.000250
AC XY:
182
AN XY:
727236
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33478
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.0000504
AC:
2
AN:
39698
South Asian (SAS)
AF:
0.00282
AC:
243
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
0.000173
AC:
1
AN:
5768
European-Non Finnish (NFE)
AF:
0.00000180
AC:
2
AN:
1111984
Other (OTH)
AF:
0.000232
AC:
14
AN:
60392
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.474
Heterozygous variant carriers
0
16
32
49
65
81
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000788
AC:
12
AN:
152306
Hom.:
0
Cov.:
32
AF XY:
0.000107
AC XY:
8
AN XY:
74482
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41570
American (AMR)
AF:
0.00
AC:
0
AN:
15296
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5184
South Asian (SAS)
AF:
0.00249
AC:
12
AN:
4826
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10624
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68020
Other (OTH)
AF:
0.00
AC:
0
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.487
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0000868
Hom.:
0
Bravo
AF:
0.0000113
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 31, 2017
Athena Diagnostics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Nephrotic syndrome, type 3 Uncertain:1
Apr 27, 2022
Fulgent Genetics, Fulgent Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not provided Benign:1
Nov 01, 2022
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
5.5
Mutation Taster
=81/19
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

Publications

Other links and lift over

dbSNP: rs771798085; hg19: chr10-96084778; API