rs2851060

Variant names:

• chr4-101032165-C-A
• rs2851060
• NM_000944.5:c.1339+102G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-101032165-C-A
• chr4-101032165-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000944.5(PPP3CA):​c.1339+102G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PPP3CA NM_000944.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.335
• Publications: 9 publications found

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]

PPP3CA Gene-Disease associations (from GenCC):

• arthrogryposis, cleft palate, craniosynostosis, and impaired intellectual development

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• developmental and epileptic encephalopathy 91

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000944.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP3CA	NM_000944.5	MANE Select	c.1339+102G>T		intron	N/A	NP_000935.1
	PPP3CA	NM_001130691.2		c.1339+102G>T		intron	N/A	NP_001124163.1
	PPP3CA	NM_001130692.2		c.1213+102G>T		intron	N/A	NP_001124164.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP3CA	ENST00000394854.8	TSL:1 MANE Select	c.1339+102G>T		intron	N/A	ENSP00000378323.3
	PPP3CA	ENST00000394853.8	TSL:1	c.1339+102G>T		intron	N/A	ENSP00000378322.4
	PPP3CA	ENST00000323055.10	TSL:1	c.1213+102G>T		intron	N/A	ENSP00000320580.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 737042 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 363800

African (AFR) AF: 0.00 AC: 0 AN: 15334

American (AMR) AF: 0.00 AC: 0 AN: 11808

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13308

East Asian (EAS) AF: 0.00 AC: 0 AN: 26712

South Asian (SAS) AF: 0.00 AC: 0 AN: 28346

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37916

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3940

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 566488

Other (OTH) AF: 0.00 AC: 0 AN: 33190

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 132299

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	5.4
DANN	Benign	0.82
PhyloP100		-0.34

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

Other links and lift over

dbSNP: rs2851060; hg19: chr4-101953322;