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GeneBe

4-101025858-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000944.5(PPP3CA):c.*7C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 1,058,810 control chromosomes in the GnomAD database, including 121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0083 ( 14 hom., cov: 29)
Exomes 𝑓: 0.012 ( 107 hom. )

Consequence

PPP3CA
NM_000944.5 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.69
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 4-101025858-G-T is Benign according to our data. Variant chr4-101025858-G-T is described in ClinVar as [Benign]. Clinvar id is 1695101.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1158 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PPP3CANM_000944.5 linkuse as main transcriptc.*7C>A 3_prime_UTR_variant 14/14 ENST00000394854.8
PPP3CANM_001130691.2 linkuse as main transcriptc.*7C>A 3_prime_UTR_variant 13/13
PPP3CANM_001130692.2 linkuse as main transcriptc.*7C>A 3_prime_UTR_variant 12/12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PPP3CAENST00000394854.8 linkuse as main transcriptc.*7C>A 3_prime_UTR_variant 14/141 NM_000944.5 P3Q08209-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00829
AC:
1158
AN:
139742
Hom.:
14
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.00139
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00557
Gnomad ASJ
AF:
0.00118
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00116
Gnomad FIN
AF:
0.0478
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0100
Gnomad OTH
AF:
0.00622
GnomAD3 exomes
AF:
0.0102
AC:
2017
AN:
198388
Hom.:
26
AF XY:
0.0100
AC XY:
1090
AN XY:
108478
show subpopulations
Gnomad AFR exome
AF:
0.00171
Gnomad AMR exome
AF:
0.00280
Gnomad ASJ exome
AF:
0.00148
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000675
Gnomad FIN exome
AF:
0.0455
Gnomad NFE exome
AF:
0.0104
Gnomad OTH exome
AF:
0.0109
GnomAD4 exome
AF:
0.0120
AC:
11017
AN:
919020
Hom.:
107
Cov.:
26
AF XY:
0.0115
AC XY:
5360
AN XY:
464856
show subpopulations
Gnomad4 AFR exome
AF:
0.00168
Gnomad4 AMR exome
AF:
0.00339
Gnomad4 ASJ exome
AF:
0.00143
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000929
Gnomad4 FIN exome
AF:
0.0494
Gnomad4 NFE exome
AF:
0.0121
Gnomad4 OTH exome
AF:
0.00967
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00828
AC:
1158
AN:
139790
Hom.:
14
Cov.:
29
AF XY:
0.00920
AC XY:
618
AN XY:
67168
show subpopulations
Gnomad4 AFR
AF:
0.00139
Gnomad4 AMR
AF:
0.00557
Gnomad4 ASJ
AF:
0.00118
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00116
Gnomad4 FIN
AF:
0.0478
Gnomad4 NFE
AF:
0.0100
Gnomad4 OTH
AF:
0.00617
Alfa
AF:
0.00759
Hom.:
10
Bravo
AF:
0.00540
Asia WGS
AF:
0.000578
AC:
2
AN:
3476

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenApr 01, 2024PPP3CA: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.49
Cadd
Benign
16
Dann
Benign
0.77

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs114065681; hg19: chr4-101947015; API