GeneBe

rs35434632

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_000944.5(PPP3CA):​c.*27_*44delTTTTTTTTTTTTTTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000334 in 479,362 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000029 ( 0 hom., cov: 0)
Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

PPP3CA
NM_000944.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.89

Publications

1 publications found
Variant links:
Genes affected
PPP3CA (HGNC:9314): (protein phosphatase 3 catalytic subunit alpha) Enables several functions, including ATPase binding activity; calmodulin binding activity; and calmodulin-dependent protein phosphatase activity. Involved in several processes, including calcineurin-NFAT signaling cascade; peptidyl-serine dephosphorylation; and response to calcium ion. Located in several cellular components, including cytosol; dendritic spine; and nucleoplasm. Part of calcineurin complex. Colocalizes with cytoplasmic side of plasma membrane. Implicated in developmental and epileptic encephalopathy 91. Biomarker of focal segmental glomerulosclerosis and schizophrenia. [provided by Alliance of Genome Resources, Apr 2022]
PPP3CA Gene-Disease associations (from GenCC):
  • arthrogryposis, cleft palate, craniosynostosis, and impaired intellectual development
    Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
  • developmental and epileptic encephalopathy 91
    Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
  • autosomal dominant non-syndromic intellectual disability
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • undetermined early-onset epileptic encephalopathy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2
High AC in GnomAdExome4 at 15 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000944.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
PPP3CA
NM_000944.5
MANE Select
c.*27_*44delTTTTTTTTTTTTTTTTTT
3_prime_UTR
Exon 14 of 14NP_000935.1Q08209-1
PPP3CA
NM_001130691.2
c.*27_*44delTTTTTTTTTTTTTTTTTT
3_prime_UTR
Exon 13 of 13NP_001124163.1Q08209-2
PPP3CA
NM_001130692.2
c.*27_*44delTTTTTTTTTTTTTTTTTT
3_prime_UTR
Exon 12 of 12NP_001124164.1Q08209-3

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
PPP3CA
ENST00000394854.8
TSL:1 MANE Select
c.*27_*44delTTTTTTTTTTTTTTTTTT
3_prime_UTR
Exon 14 of 14ENSP00000378323.3Q08209-1
PPP3CA
ENST00000394853.8
TSL:1
c.*27_*44delTTTTTTTTTTTTTTTTTT
3_prime_UTR
Exon 13 of 13ENSP00000378322.4Q08209-2
PPP3CA
ENST00000323055.10
TSL:1
c.*27_*44delTTTTTTTTTTTTTTTTTT
3_prime_UTR
Exon 12 of 12ENSP00000320580.6Q08209-3

Frequencies

GnomAD3 genomes
AF:
0.0000289
AC:
1
AN:
34564
Hom.:
0
Cov.:
0
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:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000466
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000337
AC:
15
AN:
444798
Hom.:
0
AF XY:
0.0000478
AC XY:
11
AN XY:
230308
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
10440
American (AMR)
AF:
0.0000616
AC:
1
AN:
16238
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
7394
East Asian (EAS)
AF:
0.00
AC:
0
AN:
15140
South Asian (SAS)
AF:
0.000200
AC:
7
AN:
34952
European-Finnish (FIN)
AF:
0.0000422
AC:
1
AN:
23676
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
1540
European-Non Finnish (NFE)
AF:
0.0000189
AC:
6
AN:
317874
Other (OTH)
AF:
0.00
AC:
0
AN:
17544
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.632
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome 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
GnomAD4 genome
AF:
0.0000289
AC:
1
AN:
34564
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
15202
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
7946
American (AMR)
AF:
0.00
AC:
0
AN:
1870
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
1164
East Asian (EAS)
AF:
0.00
AC:
0
AN:
442
South Asian (SAS)
AF:
0.00
AC:
0
AN:
538
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
344
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
30
European-Non Finnish (NFE)
AF:
0.0000466
AC:
1
AN:
21438
Other (OTH)
AF:
0.00
AC:
0
AN:
398
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
53

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
PhyloP100
1.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs35434632; hg19: chr4-101946977; API