2-55564382-G-T

Position:

• chr2-55564382-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001122964.3(PPP4R3B):​c.2191C>A​(p.Pro731Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPP4R3B NM_001122964.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.46

Genes affected

PPP4R3B (HGNC:29267): (protein phosphatase 4 regulatory subunit 3B) Predicted to act upstream of or within positive regulation of gluconeogenesis and protein dephosphorylation. Located in centrosome and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13055491).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP4R3B	NM_001122964.3	c.2191C>A	p.Pro731Thr	missense_variant	15/17	ENST00000616407.2	NP_001116436.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP4R3B	ENST00000616407.2	c.2191C>A	p.Pro731Thr	missense_variant	15/17	1	NM_001122964.3	ENSP00000483228.1
PPP4R3B	ENST00000616288.4	c.2095C>A	p.Pro699Thr	missense_variant	14/16	1		ENSP00000484116.1
PPP4R3B	ENST00000611717.4	c.1936C>A	p.Pro646Thr	missense_variant	13/15	1		ENSP00000478677.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251176 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135762

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 12, 2024

The c.2191C>A (p.P731T) alteration is located in exon 15 (coding exon 15) of the PPP4R3B gene. This alteration results from a C to A substitution at nucleotide position 2191, causing the proline (P) at amino acid position 731 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.099	.;.;T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.093
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	.;.;M
PrimateAI	Benign	0.44	T
Sift4G	Benign	0.14	T;T;T
Polyphen		0.073	B;B;B
Vest4		0.37
MutPred		0.33		.;.;Gain of phosphorylation at P731 (P = 0.0092);
MVP		0.043
ClinPred		0.87	D
GERP RS		4.2
Varity_R		0.066
gMVP		0.52

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: rs1239809309; hg19: chr2-55791518;