4-101170174-CAAAAG-C

Position:

• chr4-101170174-CAAAAG-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000944.5(PPP3CA):​c.259+25737_259+25741del variant causes a intron 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 0.49 (19326 hom., cov: 0)
• Consequence: PPP3CA NM_000944.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.426

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP3CA	NM_000944.5	c.259+25737_259+25741del		intron_variant		ENST00000394854.8	NP_000935.1
PPP3CA	NM_001130691.2	c.259+25737_259+25741del		intron_variant			NP_001124163.1
PPP3CA	NM_001130692.2	c.259+25737_259+25741del		intron_variant			NP_001124164.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP3CA	ENST00000394854.8	c.259+25737_259+25741del		intron_variant		1	NM_000944.5	ENSP00000378323	P3

Frequencies

GnomAD3 genomes AF: 0.488 AC: 73810 AN: 151212 Hom.: 19324 Cov.: 0

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.712

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.498

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.488 AC: 73804 AN: 151328 Hom.: 19326 Cov.: 0 AF XY: 0.485 AC XY: 35857 AN XY: 73890

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.432

Gnomad4 EAS AF: 0.284

Gnomad4 SAS AF: 0.492

Gnomad4 FIN AF: 0.629

Gnomad4 NFE AF: 0.604

Gnomad4 OTH AF: 0.493

Alfa AF: 0.544 Hom.: 2842

Bravo AF: 0.457

Asia WGS AF: 0.392 AC: 1358 AN: 3464

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: rs45625639; hg19: chr4-102091331;