2-55549981-T-A

Position:

• chr2-55549981-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001122964.3(PPP4R3B):​c.2480A>T​(p.Tyr827Phe) 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: 32)
• Consequence: PPP4R3B NM_001122964.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.83

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30048317).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP4R3B	NM_001122964.3	c.2480A>T	p.Tyr827Phe	missense_variant	17/17	ENST00000616407.2	NP_001116436.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP4R3B	ENST00000616407.2	c.2480A>T	p.Tyr827Phe	missense_variant	17/17	1	NM_001122964.3	ENSP00000483228.1
PPP4R3B	ENST00000616288.4	c.2384A>T	p.Tyr795Phe	missense_variant	16/16	1		ENSP00000484116.1
PPP4R3B	ENST00000611717.4	c.2225A>T	p.Tyr742Phe	missense_variant	15/15	1		ENSP00000478677.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Dec 18, 2023

The c.2480A>T (p.Y827F) alteration is located in exon 17 (coding exon 17) of the PPP4R3B gene. This alteration results from a A to T substitution at nucleotide position 2480, causing the tyrosine (Y) at amino acid position 827 to be replaced by a phenylalanine (F). 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	Pathogenic	0.72
BayesDel_addAF	Uncertain	0.080	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	.;.;T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Uncertain	2.6	.;.;M
PrimateAI	Uncertain	0.74	T
Sift4G	Uncertain	0.026	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.48
MutPred		0.37		.;.;Loss of phosphorylation at Y827 (P = 0.0497);
MVP		0.18
ClinPred		0.96	D
GERP RS		5.4
Varity_R		0.40
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr2-55777117;