rs67319648

Positions:

• chr10-120457350-C-G
• chr10-120457350-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001030059.3(PLPP4):​c.45C>G​(p.Phe15Leu) 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. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PLPP4 NM_001030059.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300

Genes affected

PLPP4 (HGNC:23531): (phospholipid phosphatase 4) Enables diacylglycerol diphosphate phosphatase activity; identical protein binding activity; and phosphatidate phosphatase activity. Involved in phospholipid dephosphorylation and regulation of calcium ion import. Predicted to be located in plasma membrane. Biomarker of breast cancer. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22407007).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLPP4	NM_001030059.3	c.45C>G	p.Phe15Leu	missense_variant	1/7	ENST00000398250.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLPP4	ENST00000398250.6	c.45C>G	p.Phe15Leu	missense_variant	1/7	1	NM_001030059.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	20
DANN	Benign	0.94
DEOGEN2	Benign	0.035	T;.
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.68	T;T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.74	N;N;N;N
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.14
Sift	Benign	0.51	T;T
Sift4G	Benign	0.91	T;T
Polyphen		0.0010	B;.
Vest4		0.43
MutPred		0.42		Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);
MVP		0.27
MPC		0.42
ClinPred		0.22	T
GERP RS		2.9
Varity_R		0.22
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs67319648; hg19: chr10-122216862;