19-40363275-A-G

Position:

• chr19-40363275-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012268.4(PLD3):​c.-278-2443A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,080 control chromosomes in the GnomAD database, including 3,059 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 0.20 (3059 hom., cov: 32)
• Consequence: PLD3 NM_012268.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.284

Genes affected

PLD3 (HGNC:17158): (phospholipase D family member 3) This gene encodes a member of the phospholipase D (PLD) family of enzymes that catalyze the hydrolysis of membrane phospholipids. The encoded protein is a single-pass type II membrane protein and contains two PLD phosphodiesterase domains. This protein influences processing of amyloid-beta precursor protein. Mutations in this gene are associated with Alzheimer disease risk. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Apr 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLD3	NM_012268.4	c.-278-2443A>G		intron_variant		ENST00000409735.9
PLD3	NM_001031696.4	c.-98-2278A>G		intron_variant
PLD3	NM_001291311.2	c.-278-2443A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLD3	ENST00000409735.9	c.-278-2443A>G		intron_variant		1	NM_012268.4	P1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29790 AN: 151962 Hom.: 3060 Cov.: 32

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.0473

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.196 AC: 29807 AN: 152080 Hom.: 3059 Cov.: 32 AF XY: 0.196 AC XY: 14604 AN XY: 74338

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.0467

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.191

Alfa AF: 0.170 Hom.: 4694

Bravo AF: 0.203

Asia WGS AF: 0.100 AC: 347 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.0
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs10407447; hg19: chr19-40869182;