rs1469055916

Variant names:

• chr19-11359632-A-T
• rs1469055916
• NM_001393892.1:c.167A>T

Variant summary

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

The NM_001393892.1(PLPPR2):​c.167A>T​(p.Tyr56Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,460,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: PLPPR2 NM_001393892.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.35
• Publications: 0 publications found

Genes affected

PLPPR2 (HGNC:29566): (phospholipid phosphatase related 2) Predicted to enable lipid phosphatase activity and phosphatidate phosphatase activity. Predicted to be involved in phospholipid dephosphorylation; phospholipid metabolic process; and signal transduction. Predicted to be integral component of membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.13663134).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393892.1. 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
	PLPPR2	NM_001393892.1	MANE Select	c.167A>T	p.Tyr56Phe	missense	Exon 4 of 10	NP_001380821.1	A0A8I5KWF3
	PLPPR2	NM_001393893.1		c.167A>T	p.Tyr56Phe	missense	Exon 4 of 10	NP_001380822.1	A0A8I5KWF3
	PLPPR2	NM_001170635.2		c.92A>T	p.Tyr31Phe	missense	Exon 4 of 10	NP_001164106.1	Q96GM1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLPPR2	ENST00000688289.1	MANE Select	c.167A>T	p.Tyr56Phe	missense	Exon 4 of 10	ENSP00000510269.1	A0A8I5KWF3
	PLPPR2	ENST00000251473.9	TSL:1	c.167A>T	p.Tyr56Phe	missense	Exon 4 of 10	ENSP00000251473.4	Q96GM1-1
	PLPPR2	ENST00000970838.1		c.167A>T	p.Tyr56Phe	missense	Exon 3 of 9	ENSP00000640897.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 250152 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000205 AC: 30 AN: 1460790 Hom.: 0 Cov.: 31 AF XY: 0.0000206 AC XY: 15 AN XY: 726638

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44512

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.00 AC: 0 AN: 86052

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

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

European-Non Finnish (NFE) AF: 0.0000270 AC: 30 AN: 1111498

Other (OTH) AF: 0.00 AC: 0 AN: 60336

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.000164

EpiControl AF: 0.00

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	0.11
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.059
FATHMM_MKL	Benign	0.60	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.95	T
PhyloP100		1.4
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.049
Sift	Benign	0.18	T
Sift4G	Benign	0.36	T
Polyphen		0.099	B
Vest4		0.21
MutPred		0.61		Loss of phosphorylation at Y56 (P = 0.0387)
MVP		0.030
MPC		0.79
ClinPred		0.15	T
GERP RS		5.3
Varity_R		0.070
gMVP		0.85
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1469055916; hg19: chr19-11470308;