NM_147180.4:c.145C>G

Variant names:

• chr9-101594777-G-C
• rs142403692
• NM_147180.4:c.145C>G

Variant summary

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

The NM_147180.4(PPP3R2):​c.145C>G​(p.Leu49Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000128 in 1,613,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: PPP3R2 NM_147180.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.08
• Publications: 2 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_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19472092).

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.145C>G	p.Leu49Val	missense	Exon 1 of 1	NP_671709.2	Q96LZ3
	GRIN3A	NM_133445.3	MANE Select	c.2767-15417C>G		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.145C>G	p.Leu49Val	missense	Exon 1 of 1	ENSP00000363939.2	Q96LZ3
	GRIN3A	ENST00000361820.6	TSL:1 MANE Select	c.2767-15417C>G		intron	N/A	ENSP00000355155.3	Q8TCU5
	PPP3R2	ENST00000636434.1	TSL:1	c.-37+68C>G		intron	N/A	ENSP00000490051.1	A0A1B0GUC7

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000482

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: 0.00316

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000179 AC: 45 AN: 251070 AF XY: 0.000199

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000193

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000129 AC: 188 AN: 1461542 Hom.: 0 Cov.: 31 AF XY: 0.000147 AC XY: 107 AN XY: 727082

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

American (AMR) AF: 0.000402 AC: 18 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: 0.000290 AC: 25 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53088

Middle Eastern (MID) AF: 0.00260 AC: 15 AN: 5768

European-Non Finnish (NFE) AF: 0.000104 AC: 116 AN: 1111996

Other (OTH) AF: 0.000182 AC: 11 AN: 60392

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152308 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74482

African (AFR) AF: 0.0000481 AC: 2 AN: 41580

American (AMR) AF: 0.000196 AC: 3 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68028

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.000121

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000206 AC: 25

EpiCase AF: 0.000382

EpiControl AF: 0.000415

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	Benign	0.34
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Benign	0.60
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.65
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.63	T
PhyloP100		2.1
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.14
Sift	Benign	0.23	T
Sift4G	Benign	0.21	T
Vest4		0.32
MVP		0.65
MPC		0.42
ClinPred		0.053	T
GERP RS		-0.077
PromoterAI		-0.020	Neutral
Mutation Taster		=84/16	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: rs142403692; hg19: chr9-104357059;