2-55617180-T-C

Variant names:

• chr2-55617180-T-C
• rs199629271
• NM_001122964.3:c.106A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001122964.3(PPP4R3B):​c.106A>G​(p.Lys36Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: PPP4R3B NM_001122964.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.94
• Publications: 3 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10075906).

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.106A>G	p.Lys36Glu	missense	Exon 1 of 17	NP_001116436.3	Q5MIZ7-1
	PPP4R3B	NM_001282850.2		c.106A>G	p.Lys36Glu	missense	Exon 1 of 16	NP_001269779.1	Q5MIZ7-2
	PPP4R3B	NM_020463.4		c.106A>G	p.Lys36Glu	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.106A>G	p.Lys36Glu	missense	Exon 1 of 17	ENSP00000483228.1	Q5MIZ7-1
	PPP4R3B	ENST00000616288.4	TSL:1	c.106A>G	p.Lys36Glu	missense	Exon 1 of 16	ENSP00000484116.1	Q5MIZ7-2
	PPP4R3B	ENST00000611717.4	TSL:1	c.106A>G	p.Lys36Glu	missense	Exon 1 of 15	ENSP00000478677.1	Q5MIZ7-3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152102 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251094 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000164

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152220 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74422

African (AFR) AF: 0.00 AC: 0 AN: 41544

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000247 AC: 3

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	Benign	0.23
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.044	T
Eigen	Benign	-0.15
Eigen_PC	Benign	0.098
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		7.9
PrimateAI	Pathogenic	0.84	D
Sift4G	Benign	0.68	T
Polyphen		0.0	B
Vest4		0.54
MVP		0.068
ClinPred		0.58	D
GERP RS		5.2
PromoterAI		-0.026	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.65
gMVP		0.37
Mutation Taster		=99/1	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

dbSNP: rs199629271; hg19: chr2-55844316; COSMIC: COSV55401706; COSMIC: COSV55401706;