4-101025820-CAAAAAAAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAAAA

Variant names:

• chr4-101025820-C-CAA
• rs35434632
• NM_000944.5:c.*43_*44dupTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_000944.5(PPP3CA):​c.*43_*44dupTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0048 (0 hom.)
• Consequence: PPP3CA NM_000944.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 50 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP3CA	NM_000944.5	c.*43_*44dupTT		3_prime_UTR_variant	Exon 14 of 14	ENST00000394854.8	NP_000935.1
PPP3CA	NM_001130691.2	c.*43_*44dupTT		3_prime_UTR_variant	Exon 13 of 13		NP_001124163.1
PPP3CA	NM_001130692.2	c.*43_*44dupTT		3_prime_UTR_variant	Exon 12 of 12		NP_001124164.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP3CA	ENST00000394854	c.*43_*44dupTT		3_prime_UTR_variant	Exon 14 of 14	1	NM_000944.5	ENSP00000378323.3

Frequencies

GnomAD3 genomes AF: 0.00145 AC: 50 AN: 34558 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00160

Gnomad ASJ AF: 0.000859

Gnomad EAS AF: 0.00455

Gnomad SAS AF: 0.00558

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00149

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00475 AC: 2109 AN: 443964 Hom.: 0 Cov.: 0 AF XY: 0.00481 AC XY: 1106 AN XY: 229910

Gnomad4 AFR exome AF: 0.00393

Gnomad4 AMR exome AF: 0.00512

Gnomad4 ASJ exome AF: 0.00677

Gnomad4 EAS exome AF: 0.00874

Gnomad4 SAS exome AF: 0.00776

Gnomad4 FIN exome AF: 0.00296

Gnomad4 NFE exome AF: 0.00432

Gnomad4 OTH exome AF: 0.00474

GnomAD4 genome AF: 0.00145 AC: 50 AN: 34594 Hom.: 0 Cov.: 0 AF XY: 0.00151 AC XY: 23 AN XY: 15224

Gnomad4 AFR AF: 0.00113

Gnomad4 AMR AF: 0.00160

Gnomad4 ASJ AF: 0.000859

Gnomad4 EAS AF: 0.00450

Gnomad4 SAS AF: 0.00556

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00149

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;