NM_001393892.1:c.1105C>T

Variant names:

• chr19-11364436-C-T
• rs144388150
• NM_001393892.1:c.1105C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001393892.1(PLPPR2):​c.1105C>T​(p.Arg369Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,519,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R369G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: PLPPR2 NM_001393892.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.48
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12257534).

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.1105C>T	p.Arg369Cys	missense	Exon 10 of 10	NP_001380821.1	A0A8I5KWF3
	PLPPR2	NM_001393893.1		c.1105C>T	p.Arg369Cys	missense	Exon 10 of 10	NP_001380822.1	A0A8I5KWF3
	PLPPR2	NM_001170635.2		c.1030C>T	p.Arg344Cys	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.1105C>T	p.Arg369Cys	missense	Exon 10 of 10	ENSP00000510269.1	A0A8I5KWF3
	PLPPR2	ENST00000251473.9	TSL:1	c.*57C>T		3_prime_UTR	Exon 10 of 10	ENSP00000251473.4	Q96GM1-1
	PLPPR2	ENST00000970838.1		c.1105C>T	p.Arg369Cys	missense	Exon 9 of 9	ENSP00000640897.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152208 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000751 AC: 12 AN: 159744 AF XY: 0.0000705

Gnomad AFR exome AF: 0.0000734

Gnomad AMR exome AF: 0.0000932

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000116

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000127 AC: 173 AN: 1366786 Hom.: 0 Cov.: 31 AF XY: 0.000115 AC XY: 77 AN XY: 671424

African (AFR) AF: 0.00 AC: 0 AN: 30712

American (AMR) AF: 0.0000963 AC: 3 AN: 31142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20348

East Asian (EAS) AF: 0.00 AC: 0 AN: 38494

South Asian (SAS) AF: 0.00 AC: 0 AN: 72214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41560

Middle Eastern (MID) AF: 0.000372 AC: 2 AN: 5380

European-Non Finnish (NFE) AF: 0.000149 AC: 160 AN: 1070356

Other (OTH) AF: 0.000141 AC: 8 AN: 56580

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152326 Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5 AN XY: 74482

African (AFR) AF: 0.0000240 AC: 1 AN: 41584

American (AMR) AF: 0.0000653 AC: 1 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

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

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000718

ExAC AF: 0.0000669 AC: 8

Asia WGS AF: 0.000866 AC: 3 AN: 3478

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	0.31
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	25
DANN	Benign	0.92
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.12	T
PhyloP100		2.5
PrimateAI	Pathogenic	0.88	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.11	B
Vest4		0.29
MVP		0.74
MPC		1.1
GERP RS		4.2
gMVP		0.28
Mutation Taster		=88/12	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: rs144388150; hg19: chr19-11475112;