rs3739723

Positions:

• chr9-101592068-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.889

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PPP3R2	NM_147180.4	c.*2341A>T		3_prime_UTR_variant	1/1	ENST00000374806.2	NP_671709.2
GRIN3A	NM_133445.3	c.2767-12708A>T		intron_variant		ENST00000361820.6	NP_597702.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP3R2	ENST00000374806.2	c.*2341A>T		3_prime_UTR_variant	1/1		NM_147180.4	ENSP00000363939	P1
GRIN3A	ENST00000361820.6	c.2767-12708A>T		intron_variant		1	NM_133445.3	ENSP00000355155	P1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22198 AN: 152068 Hom.: 1775 Cov.: 33

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: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.146 AC: 22199 AN: 152186 Hom.: 1773 Cov.: 33 AF XY: 0.145 AC XY: 10795 AN XY: 74412

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.0741

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.0962

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.155

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

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

Other links and lift over

dbSNP: rs3739723; hg19: chr9-104354350;