rs687

Positions:

• chr2-68188635-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_000945.4(PPP3R1):​c.99C>T​(p.Asp33=) variant causes a synonymous change. The variant allele was found at a frequency of 0.429 in 1,611,810 control chromosomes in the GnomAD database, including 152,011 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.46 (16010 hom., cov: 31)
  • Exomes 𝑓: 0.43 (136001 hom.)
• Consequence: PPP3R1 NM_000945.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.12

Genes affected

PPP3R1 (HGNC:9317): (protein phosphatase 3 regulatory subunit B, alpha) Enables cyclosporin A binding activity; phosphatase binding activity; and protein domain specific binding activity. Involved in calcineurin-NFAT signaling cascade and positive regulation of transcription by RNA polymerase II. Part of calcineurin complex. Implicated in Alzheimer's disease and dilated cardiomyopathy. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 2-68188635-G-A is Benign according to our data. Variant chr2-68188635-G-A is described in ClinVar as [Benign]. Clinvar id is 1181494.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP3R1	NM_000945.4	c.99C>T	p.Asp33=	synonymous_variant	3/6	ENST00000234310.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP3R1	ENST00000234310.8	c.99C>T	p.Asp33=	synonymous_variant	3/6	1	NM_000945.4	P1
PPP3R1	ENST00000409752.5	c.156C>T	p.Asp52=	synonymous_variant	3/6	3
PPP3R1	ENST00000409377.1	c.69C>T	p.Asp23=	synonymous_variant	3/6	3

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69109 AN: 151774 Hom.: 15994 Cov.: 31

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.473

GnomAD3 exomes AF: 0.473 AC: 117015 AN: 247438 Hom.: 28599 AF XY: 0.480 AC XY: 64440 AN XY: 134372

Gnomad AFR exome AF: 0.493

Gnomad AMR exome AF: 0.471

Gnomad ASJ exome AF: 0.461

Gnomad EAS exome AF: 0.514

Gnomad SAS exome AF: 0.635

Gnomad FIN exome AF: 0.538

Gnomad NFE exome AF: 0.408

Gnomad OTH exome AF: 0.481

GnomAD4 exome AF: 0.426 AC: 621984 AN: 1459918 Hom.: 136001 Cov.: 37 AF XY: 0.432 AC XY: 314112 AN XY: 726282

Gnomad4 AFR exome AF: 0.497

Gnomad4 AMR exome AF: 0.471

Gnomad4 ASJ exome AF: 0.458

Gnomad4 EAS exome AF: 0.475

Gnomad4 SAS exome AF: 0.632

Gnomad4 FIN exome AF: 0.535

Gnomad4 NFE exome AF: 0.397

Gnomad4 OTH exome AF: 0.447

GnomAD4 genome AF: 0.455 AC: 69174 AN: 151892 Hom.: 16010 Cov.: 31 AF XY: 0.464 AC XY: 34425 AN XY: 74238

Gnomad4 AFR AF: 0.492

Gnomad4 AMR AF: 0.477

Gnomad4 ASJ AF: 0.460

Gnomad4 EAS AF: 0.506

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.538

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.478

Alfa AF: 0.421 Hom.: 8959

Bravo AF: 0.447

Asia WGS AF: 0.586 AC: 2032 AN: 3472

EpiCase AF: 0.418

EpiControl AF: 0.411

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

Jun 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	11
DANN	Benign	0.64

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: rs687; hg19: chr2-68415767; COSMIC: COSV52246314;