X-341404-G-C

Variant names:

• chrX-341404-G-C
• rs2738364
• ENST00000477110.6:n.938C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000477110.6(PPP2R3B):​n.938C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 1,611,780 control chromosomes in the GnomAD database, including 513,198 homozygotes. There are 638,742 hemizygotes in GnomAD. 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 0.80 (48997 hom., 59354 hem., cov: 34)
  • Exomes 𝑓: 0.80 (464201 hom. 579388 hem.)
• Consequence: PPP2R3B ENST00000477110.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190
• Publications: 0 publications found

Genes affected

PPP2R3B (HGNC:13417): (protein phosphatase 2 regulatory subunit B''beta) Protein phosphatase 2 (formerly named type 2A) is one of the four major Ser/Thr phosphatases and is implicated in the negative control of cell growth and division. Protein phosphatase 2 holoenzymes are heterotrimeric proteins composed of a structural subunit A, a catalytic subunit C, and a regulatory subunit B. The regulatory subunit is encoded by a diverse set of genes that have been grouped into the B/PR55, B'/PR61, and B''/PR72 families. These different regulatory subunits confer distinct enzymatic specificities and intracellular localizations to the holozenzyme. The product of this gene belongs to the B'' family. The B'' family has been further divided into subfamilies. The product of this gene belongs to the beta subfamily of regulatory subunit B''. [provided by RefSeq, Apr 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R3B	NM_013239.5	c.1086-8C>G		splice_region_variant, intron_variant	Intron 8 of 12	ENST00000390665.9	NP_037371.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R3B	ENST00000390665.9	c.1086-8C>G		splice_region_variant, intron_variant	Intron 8 of 12	1	NM_013239.5	ENSP00000375080.3

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121744 AN: 152048 Hom.: 48980 Cov.: 34

Gnomad AFR AF: 0.840

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.700

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.817

Gnomad FIN AF: 0.785

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.801

Gnomad OTH AF: 0.811

GnomAD2 exomes AF: 0.780 AC: 193521 AN: 248100 AF XY: 0.789

Gnomad AFR exome AF: 0.843

Gnomad AMR exome AF: 0.608

Gnomad ASJ exome AF: 0.798

Gnomad EAS exome AF: 0.815

Gnomad FIN exome AF: 0.790

Gnomad NFE exome AF: 0.803

Gnomad OTH exome AF: 0.803

GnomAD4 exome AF: 0.797 AC: 1162618 AN: 1459614 Hom.: 464201 Cov.: 44 AF XY: 0.798 AC XY: 579388 AN XY: 726022

African (AFR) AF: 0.845 AC: 28289 AN: 33468

American (AMR) AF: 0.619 AC: 27660 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.797 AC: 20818 AN: 26116

East Asian (EAS) AF: 0.796 AC: 31608 AN: 39684

South Asian (SAS) AF: 0.820 AC: 70686 AN: 86242

European-Finnish (FIN) AF: 0.785 AC: 41004 AN: 52202

Middle Eastern (MID) AF: 0.853 AC: 4912 AN: 5760

European-Non Finnish (NFE) AF: 0.801 AC: 889488 AN: 1111106

Other (OTH) AF: 0.798 AC: 48153 AN: 60326

GnomAD4 genome AF: 0.800 AC: 121805 AN: 152166 Hom.: 48997 Cov.: 34 AF XY: 0.798 AC XY: 59354 AN XY: 74382

African (AFR) AF: 0.840 AC: 34878 AN: 41546

American (AMR) AF: 0.699 AC: 10688 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.791 AC: 2746 AN: 3470

East Asian (EAS) AF: 0.811 AC: 4173 AN: 5148

South Asian (SAS) AF: 0.817 AC: 3941 AN: 4826

European-Finnish (FIN) AF: 0.785 AC: 8326 AN: 10610

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.801 AC: 54446 AN: 67966

Other (OTH) AF: 0.806 AC: 1702 AN: 2112

Bravo AF: 0.796

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.39
PhyloP100		0.019
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1
Mutation Taster		=11/89	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2738364; hg19: chrX-302139;