19-40366127-T-G

Variant names:

• chr19-40366127-T-G
• rs4254419
• NM_012268.4:c.-66+197T>G

Variant summary

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

The NM_012268.4(PLD3):​c.-66+197T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.852 in 362,270 control chromosomes in the GnomAD database, including 131,811 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 0.84 (53974 hom., cov: 27)
  • Exomes 𝑓: 0.86 (77837 hom.)
• Consequence: PLD3 NM_012268.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.919

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLD3	NM_012268.4	c.-66+197T>G		intron_variant	Intron 2 of 12	ENST00000409735.9	NP_036400.2
PLD3	NM_001031696.4	c.-65-292T>G		intron_variant	Intron 2 of 12		NP_001026866.1
PLD3	NM_001291311.2	c.-66+197T>G		intron_variant	Intron 2 of 12		NP_001278240.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLD3	ENST00000409735.9	c.-66+197T>G		intron_variant	Intron 2 of 12	1	NM_012268.4	ENSP00000386938.3

Frequencies

GnomAD3 genomes AF: 0.844 AC: 127607 AN: 151132 Hom.: 53937 Cov.: 27

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.920

Gnomad AMR AF: 0.882

Gnomad ASJ AF: 0.899

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.823

Gnomad FIN AF: 0.870

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.862

Gnomad OTH AF: 0.853

GnomAD4 exome AF: 0.858 AC: 180997 AN: 211020 Hom.: 77837 Cov.: 0 AF XY: 0.854 AC XY: 96343 AN XY: 112750

Gnomad4 AFR exome AF: 0.776

Gnomad4 AMR exome AF: 0.901

Gnomad4 ASJ exome AF: 0.903

Gnomad4 EAS exome AF: 0.864

Gnomad4 SAS exome AF: 0.824

Gnomad4 FIN exome AF: 0.861

Gnomad4 NFE exome AF: 0.863

Gnomad4 OTH exome AF: 0.858

GnomAD4 genome AF: 0.844 AC: 127701 AN: 151250 Hom.: 53974 Cov.: 27 AF XY: 0.847 AC XY: 62553 AN XY: 73890

Gnomad4 AFR AF: 0.788

Gnomad4 AMR AF: 0.882

Gnomad4 ASJ AF: 0.899

Gnomad4 EAS AF: 0.868

Gnomad4 SAS AF: 0.823

Gnomad4 FIN AF: 0.870

Gnomad4 NFE AF: 0.862

Gnomad4 OTH AF: 0.854

Alfa AF: 0.853 Hom.: 31980

Bravo AF: 0.843

Asia WGS AF: 0.842 AC: 2925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.3
DANN	Benign	0.59

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: rs4254419; hg19: chr19-40872034;