chr10-120519964-A-T

Variant names:

• chr10-120519964-A-T
• rs118048115
• NM_001030059.3:c.321-1007A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001030059.3(PLPP4):​c.321-1007A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 152,316 control chromosomes in the GnomAD database, including 15 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 0.012 (15 hom., cov: 32)
• Consequence: PLPP4 NM_001030059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26
• Publications: 8 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=-0.82).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0116 (1763/152316) while in subpopulation NFE AF = 0.0204 (1388/68014). AF 95% confidence interval is 0.0195. There are 15 homozygotes in GnomAd4. There are 768 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLPP4	NM_001030059.3	c.321-1007A>T		intron_variant	Intron 4 of 6	ENST00000398250.6	NP_001025230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLPP4	ENST00000398250.6	c.321-1007A>T		intron_variant	Intron 4 of 6	1	NM_001030059.3	ENSP00000381302.1
PLPP4	ENST00000369073.3	n.291-1007A>T		intron_variant	Intron 4 of 6	5

Frequencies

GnomAD3 genomes AF: 0.0116 AC: 1763 AN: 152198 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.00391

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00497

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.00838

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0204

Gnomad OTH AF: 0.00621

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0116 AC: 1763 AN: 152316 Hom.: 15 Cov.: 32 AF XY: 0.0103 AC XY: 768 AN XY: 74494

African (AFR) AF: 0.00390 AC: 162 AN: 41574

American (AMR) AF: 0.00496 AC: 76 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4818

European-Finnish (FIN) AF: 0.00838 AC: 89 AN: 10626

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

European-Non Finnish (NFE) AF: 0.0204 AC: 1388 AN: 68014

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.0175 Hom.: 4

Bravo AF: 0.0111

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.7
DANN	Benign	0.77
PhyloP100		1.3
Mutation Taster		=100/0	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: rs118048115; hg19: chr10-122279476;