4-101025820-CAAA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000944.5(PPP3CA):c.*42_*44del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0638 in 438,870 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00058 (0 hom., cov: 0)
  • Exomes 𝑓: 0.064 (6 hom.)
  • Failed GnomAD Quality Control
• Consequence: PPP3CA NM_000944.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.74

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 4-101025820-CAAA-C is Benign according to our data. Variant chr4-101025820-CAAA-C is described in ClinVar as [Benign]. Clinvar id is 1229591.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP3CA	NM_000944.5	c.*42_*44del		3_prime_UTR_variant	14/14	ENST00000394854.8
PPP3CA	NM_001130691.2	c.*42_*44del		3_prime_UTR_variant	13/13
PPP3CA	NM_001130692.2	c.*42_*44del		3_prime_UTR_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP3CA	ENST00000394854.8	c.*42_*44del		3_prime_UTR_variant	14/14	1	NM_000944.5	P3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 20 AN: 34560 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.00214

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000535

Gnomad ASJ AF: 0.000859

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0340 AC: 1445 AN: 42522 Hom.: 0 AF XY: 0.0339 AC XY: 765 AN XY: 22536

Gnomad AFR exome AF: 0.0321

Gnomad AMR exome AF: 0.0830

Gnomad ASJ exome AF: 0.0313

Gnomad EAS exome AF: 0.0572

Gnomad SAS exome AF: 0.0475

Gnomad FIN exome AF: 0.00436

Gnomad NFE exome AF: 0.0251

Gnomad OTH exome AF: 0.0489

GnomAD4 exome AF: 0.0638 AC: 28012 AN: 438870 Hom.: 6 AF XY: 0.0636 AC XY: 14434 AN XY: 227096

Gnomad4 AFR exome AF: 0.0684

Gnomad4 AMR exome AF: 0.0383

Gnomad4 ASJ exome AF: 0.0639

Gnomad4 EAS exome AF: 0.0490

Gnomad4 SAS exome AF: 0.0668

Gnomad4 FIN exome AF: 0.0506

Gnomad4 NFE exome AF: 0.0663

Gnomad4 OTH exome AF: 0.0645

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000578 AC: 20 AN: 34596 Hom.: 0 Cov.: 0 AF XY: 0.000657 AC XY: 10 AN XY: 15224

Gnomad4 AFR AF: 0.00214

Gnomad4 AMR AF: 0.000533

Gnomad4 ASJ AF: 0.000859

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00185

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs35434632; hg19: chr4-101946977;