10-120457278-A-T

Variant names:

• chr10-120457278-A-T
• rs10886691
• NM_001030059.3:c.-28A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001030059.3(PLPP4):​c.-28A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 1,469,586 control chromosomes in the GnomAD database, including 389,465 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 0.70 (37257 hom., cov: 32)
  • Exomes 𝑓: 0.73 (352208 hom.)
• Consequence: PLPP4 NM_001030059.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289
• Publications: 10 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.761 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.-28A>T		5_prime_UTR	Exon 1 of 7	NP_001025230.1	Q5VZY2-1
	PLPP4	NM_001318167.2		c.-28A>T		5_prime_UTR	Exon 1 of 5	NP_001305096.1	Q5VZY2-2
	PLPP4	NM_001318166.2		c.-28A>T		5_prime_UTR	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.-28A>T		5_prime_UTR	Exon 1 of 7	ENSP00000381302.1	Q5VZY2-1

Frequencies

GnomAD3 genomes AF: 0.697 AC: 105661 AN: 151532 Hom.: 37227 Cov.: 32

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.636

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.577

Gnomad NFE AF: 0.725

Gnomad OTH AF: 0.701

GnomAD2 exomes AF: 0.745 AC: 77408 AN: 103922 AF XY: 0.743

Gnomad AFR exome AF: 0.620

Gnomad AMR exome AF: 0.759

Gnomad ASJ exome AF: 0.712

Gnomad EAS exome AF: 0.646

Gnomad FIN exome AF: 0.813

Gnomad NFE exome AF: 0.728

Gnomad OTH exome AF: 0.707

GnomAD4 exome AF: 0.730 AC: 962307 AN: 1317944 Hom.: 352208 Cov.: 30 AF XY: 0.731 AC XY: 473921 AN XY: 648644

African (AFR) AF: 0.616 AC: 16784 AN: 27252

American (AMR) AF: 0.753 AC: 21327 AN: 28334

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 16500 AN: 23152

East Asian (EAS) AF: 0.641 AC: 18391 AN: 28690

South Asian (SAS) AF: 0.774 AC: 53914 AN: 69644

European-Finnish (FIN) AF: 0.808 AC: 36973 AN: 45764

Middle Eastern (MID) AF: 0.610 AC: 3242 AN: 5318

European-Non Finnish (NFE) AF: 0.731 AC: 756892 AN: 1035822

Other (OTH) AF: 0.709 AC: 38284 AN: 53968

GnomAD4 genome AF: 0.697 AC: 105738 AN: 151642 Hom.: 37257 Cov.: 32 AF XY: 0.703 AC XY: 52076 AN XY: 74112

African (AFR) AF: 0.614 AC: 25421 AN: 41424

American (AMR) AF: 0.720 AC: 10985 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.705 AC: 2438 AN: 3460

East Asian (EAS) AF: 0.636 AC: 3227 AN: 5072

South Asian (SAS) AF: 0.782 AC: 3768 AN: 4818

European-Finnish (FIN) AF: 0.809 AC: 8482 AN: 10484

Middle Eastern (MID) AF: 0.573 AC: 165 AN: 288

European-Non Finnish (NFE) AF: 0.725 AC: 49158 AN: 67820

Other (OTH) AF: 0.704 AC: 1478 AN: 2100

Alfa AF: 0.664 Hom.: 3753

Bravo AF: 0.685

Asia WGS AF: 0.703 AC: 2442 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	11
DANN	Benign	0.52
PhyloP100		-0.29
PromoterAI		-0.12	Neutral
Mutation Taster		=139/161	disease causing

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: rs10886691; hg19: chr10-122216790; COSMIC: COSV68040787;