chr4-101025857-G-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_000944.5(PPP3CA):c.*8C>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00132 in 1,109,424 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0053 ( 6 hom., cov: 29)
Exomes 𝑓: 0.00071 ( 5 hom. )
Consequence
PPP3CA
NM_000944.5 3_prime_UTR
NM_000944.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.56
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
Variant 4-101025857-G-A is Benign according to our data. Variant chr4-101025857-G-A is described in ClinVar as [Benign]. Clinvar id is 3044125.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00533 (779/146150) while in subpopulation AFR AF= 0.0185 (733/39640). AF 95% confidence interval is 0.0174. There are 6 homozygotes in gnomad4. There are 365 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
BS2
?
High AC in GnomAd at 777 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PPP3CA | NM_000944.5 | c.*8C>T | 3_prime_UTR_variant | 14/14 | ENST00000394854.8 | ||
PPP3CA | NM_001130691.2 | c.*8C>T | 3_prime_UTR_variant | 13/13 | |||
PPP3CA | NM_001130692.2 | c.*8C>T | 3_prime_UTR_variant | 12/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PPP3CA | ENST00000394854.8 | c.*8C>T | 3_prime_UTR_variant | 14/14 | 1 | NM_000944.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00532 AC: 777AN: 146082Hom.: 6 Cov.: 29
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GnomAD3 exomes AF: 0.00168 AC: 313AN: 186662Hom.: 1 AF XY: 0.00112 AC XY: 115AN XY: 102472
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GnomAD4 exome AF: 0.000706 AC: 680AN: 963274Hom.: 5 Cov.: 26 AF XY: 0.000605 AC XY: 292AN XY: 483036
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
PPP3CA-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 20, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at