rs1407877

chr9-101593173-C-T

Variant summary

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

The NM_147180.4(PPP3R2):c.*1236G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,176 control chromosomes in the GnomAD database, including 1,407 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 0.12 (1407 hom., cov: 32)
  • 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: -0.108

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP3R2	NM_147180.4	c.*1236G>A		3_prime_UTR_variant	1/1	ENST00000374806.2
GRIN3A	NM_133445.3	c.2767-13813G>A		intron_variant		ENST00000361820.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP3R2	ENST00000374806.2	c.*1236G>A		3_prime_UTR_variant	1/1		NM_147180.4	P1
GRIN3A	ENST00000361820.6	c.2767-13813G>A		intron_variant		1	NM_133445.3	P1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18586 AN: 152058 Hom.: 1398 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.0764

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0904

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.0841

Gnomad OTH AF: 0.121

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 OTH exome AF: 0.00

GnomAD4 genome AF: 0.122 AC: 18607 AN: 152176 Hom.: 1407 Cov.: 32 AF XY: 0.124 AC XY: 9211 AN XY: 74408

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.0764

Gnomad4 EAS AF: 0.293

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.0904

Gnomad4 NFE AF: 0.0841

Gnomad4 OTH AF: 0.126

Alfa AF: 0.0927 Hom.: 1096

Bravo AF: 0.128

Asia WGS AF: 0.187 AC: 647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.2
Dann	Benign	0.40

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: rs1407877; hg19: chr9-104355455;