19-11364497-C-A

Variant names:

• chr19-11364497-C-A
• rs199560592
• NM_001393892.1:c.1166C>A

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.1166C>A​(p.Thr389Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T389I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PLPPR2 NM_001393892.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46
• 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=0.08667812).

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.1166C>A	p.Thr389Asn	missense	Exon 10 of 10	NP_001380821.1	A0A8I5KWF3
	PLPPR2	NM_001393893.1		c.1166C>A	p.Thr389Asn	missense	Exon 10 of 10	NP_001380822.1	A0A8I5KWF3
	PLPPR2	NM_001170635.2		c.1091C>A	p.Thr364Asn	missense	Exon 10 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.1166C>A	p.Thr389Asn	missense	Exon 10 of 10	ENSP00000510269.1	A0A8I5KWF3
	PLPPR2	ENST00000251473.9	TSL:1	c.*118C>A		3_prime_UTR	Exon 10 of 10	ENSP00000251473.4	Q96GM1-1
	PLPPR2	ENST00000970838.1		c.1166C>A	p.Thr389Asn	missense	Exon 9 of 9	ENSP00000640897.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1369102 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 674262

African (AFR) AF: 0.00 AC: 0 AN: 31352

American (AMR) AF: 0.00 AC: 0 AN: 34000

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23472

East Asian (EAS) AF: 0.00 AC: 0 AN: 35730

South Asian (SAS) AF: 0.00 AC: 0 AN: 76360

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5588

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1071084

Other (OTH) AF: 0.00 AC: 0 AN: 57190

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	22
DANN	Benign	0.88
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.087	T
PhyloP100		2.5
PrimateAI	Uncertain	0.77	T
Sift4G	Benign	0.078	T
Polyphen		0.0	B
Vest4		0.24
MVP		0.47
MPC		0.81
GERP RS		1.0
gMVP		0.087
Mutation Taster		=94/6	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: rs199560592; hg19: chr19-11475173;