rs4819

Positions:

chr19-40378026-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000409735.9(PLD3):c.1326G>A(p.Ala442=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0156 in 1,613,498 control chromosomes in the GnomAD database, including 242 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 27 hom., cov: 32)

Exomes 𝑓: 0.016 ( 215 hom. )

Consequence

PLD3
ENST00000409735.9 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -3.66

Variant links:

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]

PLD3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 19-40378026-G-A is Benign according to our data. Variant chr19-40378026-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 403325.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40378026-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.66 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0132 (2003/152238) while in subpopulation AMR AF= 0.0267 (408/15294). AF 95% confidence interval is 0.0245. There are 27 homozygotes in gnomad4. There are 1004 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2003 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PLD3	NM_012268.4 linkuse as main transcript	c.1326G>A	p.Ala442=	synonymous_variant	13/13	ENST00000409735.9	NP_036400.2
PLD3	NM_001031696.4 linkuse as main transcript	c.1326G>A	p.Ala442=	synonymous_variant	13/13		NP_001026866.1
PLD3	NM_001291311.2 linkuse as main transcript	c.1326G>A	p.Ala442=	synonymous_variant	13/13		NP_001278240.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLD3	ENST00000409735.9 linkuse as main transcript	c.1326G>A	p.Ala442=	synonymous_variant	13/13	1	NM_012268.4	ENSP00000386938	P1

Frequencies

GnomAD3 genomes

AF:

0.0131

AC:

2000

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00504

Gnomad AMI

AF:

0.0176

Gnomad AMR

AF:

0.0266

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00424

Gnomad SAS

AF:

0.0110

Gnomad FIN

AF:

0.00960

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0172

Gnomad OTH

AF:

0.00765

GnomAD3 exomes

AF:

0.0133

AC:

3327

AN:

250520

Hom.:

AF XY:

0.0133

AC XY:

1796

AN XY:

135414

show subpopulations

Gnomad AFR exome

AF:

0.00505

Gnomad AMR exome

AF:

0.0225

Gnomad ASJ exome

AF:

0.00100

Gnomad EAS exome

AF:

0.00533

Gnomad SAS exome

AF:

0.0117

Gnomad FIN exome

AF:

0.00743

Gnomad NFE exome

AF:

0.0156

Gnomad OTH exome

AF:

0.0124

GnomAD4 exome

AF:

0.0159

AC:

23175

AN:

1461260

Hom.:

215

Cov.:

AF XY:

0.0154

AC XY:

11219

AN XY:

726924

show subpopulations

Gnomad4 AFR exome

AF:

0.00433

Gnomad4 AMR exome

AF:

0.0217

Gnomad4 ASJ exome

AF:

0.00107

Gnomad4 EAS exome

AF:

0.00395

Gnomad4 SAS exome

AF:

0.0115

Gnomad4 FIN exome

AF:

0.00846

Gnomad4 NFE exome

AF:

0.0175

Gnomad4 OTH exome

AF:

0.0160

GnomAD4 genome

AF:

0.0132

AC:

2003

AN:

152238

Hom.:

Cov.:

AF XY:

0.0135

AC XY:

1004

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00505

Gnomad4 AMR

AF:

0.0267

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00425

Gnomad4 SAS

AF:

0.0110

Gnomad4 FIN

AF:

0.00960

Gnomad4 NFE

AF:

0.0172

Gnomad4 OTH

AF:

0.00757

Alfa

AF:

0.0138

Hom.:

Bravo

AF:

0.0129

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.0140

EpiControl

AF:

0.0146

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	PLD3: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: frequency. OB 12/23/15: 1.4% in Eur chr, 14 hom in ExAC -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over