10-120457350-C-T

Variant names:

• chr10-120457350-C-T
• rs67319648
• NM_001030059.3:c.45C>T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001030059.3(PLPP4):​c.45C>T​(p.Phe15Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,532,720 control chromosomes in the GnomAD database, including 30,268 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (3002 hom., cov: 33)
  • Exomes 𝑓: 0.20 (27266 hom.)
• Consequence: PLPP4 NM_001030059.3 synonymous
• 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 Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.21).
• BP7: Synonymous conserved (PhyloP=0.03 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLPP4	NM_001030059.3	c.45C>T	p.Phe15Phe	synonymous_variant	Exon 1 of 7	ENST00000398250.6	NP_001025230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLPP4	ENST00000398250.6	c.45C>T	p.Phe15Phe	synonymous_variant	Exon 1 of 7	1	NM_001030059.3	ENSP00000381302.1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29173 AN: 151890 Hom.: 3003 Cov.: 33

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.196

GnomAD3 exomes AF: 0.188 AC: 26054 AN: 138298 Hom.: 2555 AF XY: 0.190 AC XY: 14050 AN XY: 73854

Gnomad AFR exome AF: 0.159

Gnomad AMR exome AF: 0.190

Gnomad ASJ exome AF: 0.222

Gnomad EAS exome AF: 0.269

Gnomad SAS exome AF: 0.180

Gnomad FIN exome AF: 0.128

Gnomad NFE exome AF: 0.193

Gnomad OTH exome AF: 0.193

GnomAD4 exome AF: 0.197 AC: 272009 AN: 1380708 Hom.: 27266 Cov.: 33 AF XY: 0.198 AC XY: 134561 AN XY: 680640

Gnomad4 AFR exome AF: 0.170

Gnomad4 AMR exome AF: 0.191

Gnomad4 ASJ exome AF: 0.221

Gnomad4 EAS exome AF: 0.273

Gnomad4 SAS exome AF: 0.182

Gnomad4 FIN exome AF: 0.134

Gnomad4 NFE exome AF: 0.198

Gnomad4 OTH exome AF: 0.207

GnomAD4 genome AF: 0.192 AC: 29167 AN: 152012 Hom.: 3002 Cov.: 33 AF XY: 0.189 AC XY: 14064 AN XY: 74308

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.287

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.193

Alfa AF: 0.194 Hom.: 1664

Bravo AF: 0.199

Asia WGS AF: 0.217 AC: 754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
CADD	Benign	14
DANN	Benign	0.97

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

Publications

LitVar

Other links and lift over

dbSNP: rs67319648; hg19: chr10-122216862; COSMIC: COSV68038736;