2-55617170-G-A

Variant names:

• chr2-55617170-G-A
• rs766624965
• NM_001122964.3:c.116C>T

Variant summary

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

The NM_001122964.3(PPP4R3B):​c.116C>T​(p.Ser39Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,106 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: PPP4R3B NM_001122964.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.90
• Publications: 1 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.116C>T	p.Ser39Leu	missense	Exon 1 of 17	NP_001116436.3	Q5MIZ7-1
	PPP4R3B	NM_001282850.2		c.116C>T	p.Ser39Leu	missense	Exon 1 of 16	NP_001269779.1	Q5MIZ7-2
	PPP4R3B	NM_020463.4		c.116C>T	p.Ser39Leu	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.116C>T	p.Ser39Leu	missense	Exon 1 of 17	ENSP00000483228.1	Q5MIZ7-1
	PPP4R3B	ENST00000616288.4	TSL:1	c.116C>T	p.Ser39Leu	missense	Exon 1 of 16	ENSP00000484116.1	Q5MIZ7-2
	PPP4R3B	ENST00000611717.4	TSL:1	c.116C>T	p.Ser39Leu	missense	Exon 1 of 15	ENSP00000478677.1	Q5MIZ7-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000798 AC: 2 AN: 250490 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000584

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461106 Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9 AN XY: 726956

African (AFR) AF: 0.0000299 AC: 1 AN: 33416

American (AMR) AF: 0.0000450 AC: 2 AN: 44476

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000989 AC: 11 AN: 1111728

Other (OTH) AF: 0.00 AC: 0 AN: 60338

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

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	0.70
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.36
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		9.9
PrimateAI	Pathogenic	0.81	D
Sift4G	Benign	0.17	T
Polyphen		0.93	P
Vest4		0.89
MutPred		0.52		Loss of disorder (P = 0.0429)
MVP		0.082
ClinPred		0.98	D
GERP RS		5.2
PromoterAI		-0.0010	Neutral
Varity_R		0.77
gMVP		0.55
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

dbSNP: rs766624965; hg19: chr2-55844306;