1-56500678-A-G

Variant names:

• chr1-56500678-A-G
• rs17114046
• NM_003713.5:c.811-4002T>C

Variant summary

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

The NM_003713.5(PLPP3):​c.811-4002T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,190 control chromosomes in the GnomAD database, including 1,256 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 0.12 (1256 hom., cov: 32)
• Consequence: PLPP3 NM_003713.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.293
• Publications: 30 publications found

Genes affected

PLPP3 (HGNC:9229): (phospholipid phosphatase 3) The protein encoded by this gene is a member of the phosphatidic acid phosphatase (PAP) family. PAPs convert phosphatidic acid to diacylglycerol, and function in de novo synthesis of glycerolipids as well as in receptor-activated signal transduction mediated by phospholipase D. This protein is a membrane glycoprotein localized at the cell plasma membrane. It has been shown to actively hydrolyze extracellular lysophosphatidic acid and short-chain phosphatidic acid. The expression of this gene is found to be enhanced by epidermal growth factor in Hela cells. [provided by RefSeq, Mar 2010]

ENSG00000284686 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLPP3	NM_003713.5	c.811-4002T>C		intron_variant	Intron 5 of 5	ENST00000371250.4	NP_003704.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLPP3	ENST00000371250.4	c.811-4002T>C		intron_variant	Intron 5 of 5	1	NM_003713.5	ENSP00000360296.3
ENSG00000284686	ENST00000642129.1	n.454-4002T>C		intron_variant	Intron 3 of 5			ENSP00000492927.1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18193 AN: 152072 Hom.: 1251 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.0849

Gnomad ASJ AF: 0.0916

Gnomad EAS AF: 0.0282

Gnomad SAS AF: 0.0677

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0905

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.120 AC: 18225 AN: 152190 Hom.: 1256 Cov.: 32 AF XY: 0.118 AC XY: 8797 AN XY: 74416

African (AFR) AF: 0.203 AC: 8433 AN: 41502

American (AMR) AF: 0.0848 AC: 1295 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0916 AC: 318 AN: 3470

East Asian (EAS) AF: 0.0284 AC: 147 AN: 5174

South Asian (SAS) AF: 0.0675 AC: 326 AN: 4828

European-Finnish (FIN) AF: 0.109 AC: 1162 AN: 10612

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.0905 AC: 6152 AN: 68004

Other (OTH) AF: 0.122 AC: 257 AN: 2114

Alfa AF: 0.0982 Hom.: 3179

Bravo AF: 0.123

Asia WGS AF: 0.0570 AC: 200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.50
DANN	Benign	0.26
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

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: rs17114046; hg19: chr1-56966350;