NM_001030059.3:c.45C>T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001030059.3. 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
	PLPP4	NM_001030059.3	MANE Select	c.45C>T	p.Phe15Phe	synonymous	Exon 1 of 7	NP_001025230.1	Q5VZY2-1
	PLPP4	NM_001318167.2		c.45C>T	p.Phe15Phe	synonymous	Exon 1 of 5	NP_001305096.1	Q5VZY2-2
	PLPP4	NM_001318166.2		c.45C>T	p.Phe15Phe	synonymous	Exon 1 of 6	NP_001305095.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLPP4	ENST00000398250.6	TSL:1 MANE Select	c.45C>T	p.Phe15Phe	synonymous	Exon 1 of 7	ENSP00000381302.1	Q5VZY2-1

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

GnomAD2 exomes AF: 0.188 AC: 26054 AN: 138298 AF XY: 0.190

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 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

African (AFR) AF: 0.170 AC: 5210 AN: 30568

American (AMR) AF: 0.191 AC: 6398 AN: 33502

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 5485 AN: 24802

East Asian (EAS) AF: 0.273 AC: 9223 AN: 33742

South Asian (SAS) AF: 0.182 AC: 13928 AN: 76396

European-Finnish (FIN) AF: 0.134 AC: 6471 AN: 48246

Middle Eastern (MID) AF: 0.246 AC: 1390 AN: 5654

European-Non Finnish (NFE) AF: 0.198 AC: 212019 AN: 1070482

Other (OTH) AF: 0.207 AC: 11885 AN: 57316

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

African (AFR) AF: 0.176 AC: 7316 AN: 41500

American (AMR) AF: 0.195 AC: 2978 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 790 AN: 3472

East Asian (EAS) AF: 0.287 AC: 1466 AN: 5102

South Asian (SAS) AF: 0.174 AC: 842 AN: 4830

European-Finnish (FIN) AF: 0.132 AC: 1395 AN: 10584

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13665 AN: 67928

Other (OTH) AF: 0.193 AC: 406 AN: 2106

Alfa AF: 0.196 Hom.: 2918

Bravo AF: 0.199

Asia WGS AF: 0.217 AC: 754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
CADD	Benign	14
DANN	Benign	0.97
PhyloP100		0.030
PromoterAI		-0.092	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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