NM_147180.4:c.196G>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_147180.4(PPP3R2):c.196G>A(p.Gly66Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000398 in 1,614,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00041 ( 0 hom. )

Consequence

PPP3R2
NM_147180.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.05

Publications

3 publications found

Variant links:

Genes affected

PPP3R2 (HGNC:9318): (protein phosphatase 3 regulatory subunit B, beta) Predicted to enable calcium ion binding activity and calcium-dependent protein serine/threonine phosphatase regulator activity. Predicted to be involved in regulation of catalytic activity. Predicted to act upstream of or within penetration of zona pellucida. Predicted to be located in sperm mitochondrial sheath. Predicted to be part of calcineurin complex. [provided by Alliance of Genome Resources, Apr 2022]

PPP3R2 links:

GRIN3A (HGNC:16767): (glutamate ionotropic receptor NMDA type subunit 3A) This gene encodes a subunit of the N-methyl-D-aspartate (NMDA) receptors, which belong to the superfamily of glutamate-regulated ion channels, and function in physiological and pathological processes in the central nervous system. This subunit shows greater than 90% identity to the corresponding subunit in rat. Studies in the knockout mouse deficient in this subunit suggest that this gene may be involved in the development of synaptic elements by modulating NMDA receptor activity. [provided by RefSeq, Jul 2008]

GRIN3A links:

LOC105376186 (HGNC:):

LOC105376186 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.27822983).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_147180.4. 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
	PPP3R2	NM_147180.4	MANE Select	c.196G>A	p.Gly66Ser	missense	Exon 1 of 1	NP_671709.2	Q96LZ3
	GRIN3A	NM_133445.3	MANE Select	c.2767-15366G>A		intron	N/A	NP_597702.2	Q8TCU5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PPP3R2	ENST00000374806.2	TSL:6 MANE Select	c.196G>A	p.Gly66Ser	missense	Exon 1 of 1	ENSP00000363939.2	Q96LZ3
GRIN3A	ENST00000361820.6	TSL:1 MANE Select	c.2767-15366G>A		intron	N/A	ENSP00000355155.3	Q8TCU5
PPP3R2	ENST00000636434.1	TSL:1	c.-36-69G>A		intron	N/A	ENSP00000490051.1	A0A1B0GUC7

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000617

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000179

AC:

AN:

251456

AF XY:

0.000184

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000387

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000406

AC:

593

AN:

1461872

Hom.:

Cov.:

AF XY:

0.000362

AC XY:

263

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000513

AC:

571

AN:

1112012

Other (OTH)

AF:

0.000315

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

111

148

185

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000322

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41456

American (AMR)

AF:

0.0000654

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000617

AC:

AN:

68052

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000701

Hom.:

Bravo

AF:

0.000219

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000107

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.26

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.97

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.018

MetaRNN

Benign

0.28

MetaSVM

Uncertain

-0.067

PhyloP100

6.1

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-4.3

REVEL

Uncertain

0.52

Sift

Benign

0.058

Sift4G

Benign

0.089

Vest4

0.17

MVP

0.80

MPC

0.53

ClinPred

0.45

GERP RS

3.8

PromoterAI

-0.0083

Neutral

(source)

Mutation Taster

=84/16

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over