Genetic Variant NM_147180.4:c.-5C>G (chr9-101594926-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_147180.4(PPP3R2):c.-5C>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 0.0000401 in 1,597,526 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 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

PPP3R2
NM_147180.4 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.783

Publications

0 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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08460292).

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.-5C>G		5_prime_UTR	Exon 1 of 1	NP_671709.2	Q96LZ3
	GRIN3A	NM_133445.3	MANE Select	c.2767-15566C>G		intron	N/A	NP_597702.2	Q8TCU5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PPP3R2	ENST00000374806.2	TSL:6 MANE Select	c.-5C>G	5_prime_UTR	Exon 1 of 1	ENSP00000363939.2	Q96LZ3
PPP3R2	ENST00000636434.1	TSL:1	c.-118C>G	5_prime_UTR	Exon 1 of 2	ENSP00000490051.1	A0A1B0GUC7
GRIN3A	ENST00000361820.6	TSL:1 MANE Select	c.2767-15566C>G	intron	N/A	ENSP00000355155.3	Q8TCU5

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000516

AC:

AN:

232562

AF XY:

0.0000471

show subpopulations

Gnomad AFR exome

AF:

0.000472

Gnomad AMR exome

AF:

0.0000875

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000277

AC:

AN:

1445232

Hom.:

Cov.:

AF XY:

0.0000264

AC XY:

AN XY:

719238

show subpopulations

African (AFR)

AF:

0.000598

AC:

AN:

33434

American (AMR)

AF:

0.000112

AC:

AN:

44582

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25864

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.0000698

AC:

AN:

85954

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39008

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110730

Other (OTH)

AF:

0.000133

AC:

AN:

60214

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000158

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.000481

AC:

AN:

41566

American (AMR)

AF:

0.000196

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

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:

0.000142

Hom.:

Bravo

AF:

0.000230

ESP6500AA

AF:

0.000912

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000663

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

0.13

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.95

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.23

M_CAP

Benign

0.0075

MetaRNN

Benign

0.085

MetaSVM

Benign

-0.91

PhyloP100

0.78

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.48

REVEL

Benign

0.069

Sift

Benign

0.068

Sift4G

Uncertain

0.035

Vest4

0.11

MVP

0.63

MPC

0.34

ClinPred

0.025

GERP RS

1.4

PromoterAI

-0.020

Neutral

(source)

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

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