2-55617279-C-G

Variant names:

• chr2-55617279-C-G
• NM_001122964.3:c.7G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001122964.3(PPP4R3B):​c.7G>C​(p.Asp3His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 7.39
• Publications: 0 publications found

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]

PPP4R3B-DT (HGNC:55209): (PPP4R3B divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122964.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP4R3B	NM_001122964.3	MANE Select	c.7G>C	p.Asp3His	missense	Exon 1 of 17	NP_001116436.3	Q5MIZ7-1
	PPP4R3B	NM_001282850.2		c.7G>C	p.Asp3His	missense	Exon 1 of 16	NP_001269779.1	Q5MIZ7-2
	PPP4R3B	NM_020463.4		c.7G>C	p.Asp3His	missense	Exon 1 of 15	NP_065196.1	Q5MIZ7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP4R3B	ENST00000616407.2	TSL:1 MANE Select	c.7G>C	p.Asp3His	missense	Exon 1 of 17	ENSP00000483228.1	Q5MIZ7-1
	PPP4R3B	ENST00000616288.4	TSL:1	c.7G>C	p.Asp3His	missense	Exon 1 of 16	ENSP00000484116.1	Q5MIZ7-2
	PPP4R3B	ENST00000611717.4	TSL:1	c.7G>C	p.Asp3His	missense	Exon 1 of 15	ENSP00000478677.1	Q5MIZ7-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Uncertain	0.073	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	33
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Pathogenic	0.68
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.50	D
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		7.4
PrimateAI	Pathogenic	0.90	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.95	P
Vest4		0.68
MutPred		0.38		Gain of methylation at R5 (P = 0.0913)
MVP		0.068
ClinPred		0.98	D
GERP RS		4.2
PromoterAI		-0.14	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.65
gMVP		0.41
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

hg19: chr2-55844415; COSMIC: COSV55407586; COSMIC: COSV55407586;