dbSNP rs3739723: PPP3R2:c.*2341A>T (chr9-101592068-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_147180.4(PPP3R2):c.*2341A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,186 control chromosomes in the GnomAD database, including 1,773 homozygotes. 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: 𝑓 0.15 ( 1773 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PPP3R2
NM_147180.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.889

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP3R2	NM_147180.4 link	c.*2341A>T		3_prime_UTR_variant	Exon 1 of 1	ENST00000374806.2	NP_671709.2	Q96LZ3
GRIN3A	NM_133445.3 link	c.2767-12708A>T		intron_variant	Intron 6 of 8	ENST00000361820.6	NP_597702.2	Q8TCU5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP3R2	ENST00000374806 link	c.*2341A>T		3_prime_UTR_variant	Exon 1 of 1		NM_147180.4	ENSP00000363939.2		Q96LZ3
GRIN3A	ENST00000361820.6 link	c.2767-12708A>T		intron_variant	Intron 6 of 8	1	NM_133445.3	ENSP00000355155.3		Q8TCU5

Frequencies

GnomAD3 genomes

AF:

0.146

AC:

22198

AN:

152068

Hom.:

1775

Cov.:

show subpopulations

Gnomad AFR

AF:

0.195

Gnomad AMI

AF:

0.180

Gnomad AMR

AF:

0.163

Gnomad ASJ

AF:

0.0741

Gnomad EAS

AF:

0.217

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.0962

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.119

Gnomad OTH

AF:

0.157

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

Gnomad4 AFR exome

AC:

AN:

Gnomad4 AMR exome

AC:

AN:

Gnomad4 ASJ exome

AC:

AN:

Gnomad4 EAS exome

AC:

AN:

Gnomad4 SAS exome

AC:

AN:

Gnomad4 FIN exome

AC:

AN:

Gnomad4 NFE exome

AF:

0.00

AC:

AN:

Gnomad4 Remaining exome

AC:

AN:

GnomAD4 genome

AF:

0.146

AC:

22199

AN:

152186

Hom.:

1773

Cov.:

AF XY:

0.145

AC XY:

10795

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.195

AC:

0.194514

AN:

0.194514

Gnomad4 AMR

AF:

0.163

AC:

0.162982

AN:

0.162982

Gnomad4 ASJ

AF:

0.0741

AC:

0.0740634

AN:

0.0740634

Gnomad4 EAS

AF:

0.217

AC:

0.217291

AN:

0.217291

Gnomad4 SAS

AF:

0.128

AC:

0.12796

AN:

0.12796

Gnomad4 FIN

AF:

0.0962

AC:

0.0962264

AN:

0.0962264

Gnomad4 NFE

AF:

0.119

AC:

0.11898

AN:

0.11898

Gnomad4 OTH

AF:

0.155

AC:

0.154683

AN:

0.154683

Heterozygous variant carriers

984

1968

2952

3936

4920

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

248

496

744

992

1240

<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:

0.127

Hom.:

173

Bravo

AF:

0.156

Asia WGS

AF:

0.181

AC:

629

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

4.5

DANN

Benign

0.78

Mutation Taster

=100/0

polymorphism (auto)

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over