NM_147180.4:c.187G>A

Variant names:

• chr9-101594735-C-T
• rs767514182
• NM_147180.4:c.187G>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM1 PM2 PP3_Moderate

The NM_147180.4(PPP3R2):​c.187G>A​(p.Asp63Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: PPP3R2 NM_147180.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.05
• Publications: 1 publications found

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]

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]

LOC105376186 (HGNC:):

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM1: In a binding_site (size 0) in uniprot entity CANB2_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.933

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.187G>A	p.Asp63Asn	missense	Exon 1 of 1	NP_671709.2	Q96LZ3
	GRIN3A	NM_133445.3	MANE Select	c.2767-15375G>A		intron	N/A	NP_597702.2	Q8TCU5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP3R2	ENST00000374806.2	TSL:6 MANE Select	c.187G>A	p.Asp63Asn	missense	Exon 1 of 1	ENSP00000363939.2	Q96LZ3
	GRIN3A	ENST00000361820.6	TSL:1 MANE Select	c.2767-15375G>A		intron	N/A	ENSP00000355155.3	Q8TCU5
	PPP3R2	ENST00000636434.1	TSL:1	c.-36-78G>A		intron	N/A	ENSP00000490051.1	A0A1B0GUC7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000795 AC: 2 AN: 251442 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461760 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727174

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111912

Other (OTH) AF: 0.0000331 AC: 2 AN: 60394

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	26
DANN	Uncertain	1.0
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.072	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Pathogenic	0.95	D
PhyloP100		6.1
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Pathogenic	0.74
Sift	Benign	0.038	D
Sift4G	Benign	0.080	T
Vest4		0.77
MVP		0.92
MPC		0.93
ClinPred		0.98	D
GERP RS		2.9
PromoterAI		-0.014	Neutral
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs767514182; hg19: chr9-104357017; COSMIC: COSV62455270;