Variant 14-35121968-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017917.4(PPP2R3C):c.-9A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 1,613,370 control chromosomes in the GnomAD database, including 106,571 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 11403 hom., cov: 32)

Exomes 𝑓: 0.36 ( 95168 hom. )

Consequence

PPP2R3C
NM_017917.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.27

Variant links:

Genes affected

PPP2R3C (HGNC:17485): (protein phosphatase 2 regulatory subunit B''gamma) This gene encodes a regulatory subunit of the serine/threonine phosphatase, protein phosphatase 2. This protein is localized to both nuclear and cytoplasmic regions depending on cell cycle phase. Homozygous conditional knockout mice for this gene exhibit reduced numbers and impaired proliferation of immune system B cells. This protein may regulate the expression of the P-glycoprotein ATP-binding cassette transporter through its phosphatase activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]

PPP2R3C links:

PRORP (HGNC:19958): (protein only RNase P catalytic subunit) Enables ribonuclease P activity. Involved in mitochondrial tRNA 5'-end processing. Located in mitochondrion and nucleoplasm. Part of mitochondrial ribonuclease P complex. [provided by Alliance of Genome Resources, Apr 2022]

PRORP links:

PPP2R3C (HGNC:):

PPP2R3C links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 14-35121968-T-C is Benign according to our data. Variant chr14-35121968-T-C is described in ClinVar as [Benign]. Clinvar id is 1327440.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP2R3C	NM_017917.4 linkuse as main transcript	c.-9A>G		5_prime_UTR_variant	1/13	ENST00000261475.10	NP_060387.2	Q969Q6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP2R3C	ENST00000261475.10 linkuse as main transcript	c.-9A>G		5_prime_UTR_variant	1/13	1	NM_017917.4	ENSP00000261475.5		Q969Q6-1

Frequencies

GnomAD3 genomes

AF:

0.383

AC:

58114

AN:

151874

Hom.:

11386

Cov.:

show subpopulations

Gnomad AFR

AF:

0.452

Gnomad AMI

AF:

0.252

Gnomad AMR

AF:

0.361

Gnomad ASJ

AF:

0.383

Gnomad EAS

AF:

0.418

Gnomad SAS

AF:

0.460

Gnomad FIN

AF:

0.303

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.351

Gnomad OTH

AF:

0.382

GnomAD3 exomes

AF:

0.366

AC:

91955

AN:

251302

Hom.:

17266

AF XY:

0.371

AC XY:

50343

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.455

Gnomad AMR exome

AF:

0.308

Gnomad ASJ exome

AF:

0.394

Gnomad EAS exome

AF:

0.403

Gnomad SAS exome

AF:

0.456

Gnomad FIN exome

AF:

0.303

Gnomad NFE exome

AF:

0.350

Gnomad OTH exome

AF:

0.368

GnomAD4 exome

AF:

0.358

AC:

523005

AN:

1461378

Hom.:

95168

Cov.:

AF XY:

0.361

AC XY:

262252

AN XY:

726996

show subpopulations

Gnomad4 AFR exome

AF:

0.455

Gnomad4 AMR exome

AF:

0.311

Gnomad4 ASJ exome

AF:

0.386

Gnomad4 EAS exome

AF:

0.421

Gnomad4 SAS exome

AF:

0.456

Gnomad4 FIN exome

AF:

0.309

Gnomad4 NFE exome

AF:

0.347

Gnomad4 OTH exome

AF:

0.370

GnomAD4 genome

AF:

0.383

AC:

58177

AN:

151992

Hom.:

11403

Cov.:

AF XY:

0.382

AC XY:

28370

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.452

Gnomad4 AMR

AF:

0.361

Gnomad4 ASJ

AF:

0.383

Gnomad4 EAS

AF:

0.418

Gnomad4 SAS

AF:

0.461

Gnomad4 FIN

AF:

0.303

Gnomad4 NFE

AF:

0.351

Gnomad4 OTH

AF:

0.384

Alfa

AF:

0.363

Hom.:

18085

Bravo

AF:

0.386

Asia WGS

AF:

0.441

AC:

1535

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

PPP2R3C-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 04, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Spermatogenic failure 36

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.93

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over