2-55558788-A-C

Position:

• chr2-55558788-A-C

Variant summary

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

The NM_001122964.3(PPP4R3B):​c.2441T>G​(p.Val814Gly) variant causes a missense change. 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: 33)
• Consequence: PPP4R3B NM_001122964.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.23

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=0.14267406).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP4R3B	NM_001122964.3	c.2441T>G	p.Val814Gly	missense_variant	16/17	ENST00000616407.2	NP_001116436.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP4R3B	ENST00000616407.2	c.2441T>G	p.Val814Gly	missense_variant	16/17	1	NM_001122964.3	ENSP00000483228.1
PPP4R3B	ENST00000616288.4	c.2345T>G	p.Val782Gly	missense_variant	15/16	1		ENSP00000484116.1
PPP4R3B	ENST00000611717.4	c.2186T>G	p.Val729Gly	missense_variant	14/15	1		ENSP00000478677.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Sep 29, 2023

The c.2441T>G (p.V814G) alteration is located in exon 16 (coding exon 16) of the PPP4R3B gene. This alteration results from a T to G substitution at nucleotide position 2441, causing the valine (V) at amino acid position 814 to be replaced by a glycine (G). 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	0.093
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	.;.;T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.1	.;.;M
PrimateAI	Uncertain	0.53	T
Sift4G	Benign	0.38	T;T;T
Polyphen		0.13	B;D;B
Vest4		0.47
MutPred		0.23		.;.;Loss of sheet (P = 0.007);
MVP		0.043
ClinPred		0.90	D
GERP RS		5.9
Varity_R		0.16
gMVP		0.29

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-55785924;