rs4819

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_012268.4(PLD3):c.1326G>A(p.Ala442Ala) 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
NM_012268.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.66

Publications

19 publications found

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 Gene-Disease associations (from GenCC):

spinocerebellar ataxia 46
Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

PLD3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 403325.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 2003 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLD3	NM_012268.4 link	c.1326G>A	p.Ala442Ala	synonymous_variant	Exon 13 of 13	ENST00000409735.9	NP_036400.2	Q8IV08A0A024R0Q4
PLD3	NM_001031696.4 link	c.1326G>A	p.Ala442Ala	synonymous_variant	Exon 13 of 13		NP_001026866.1	Q8IV08A0A024R0Q4
PLD3	NM_001291311.2 link	c.1326G>A	p.Ala442Ala	synonymous_variant	Exon 13 of 13		NP_001278240.1	Q8IV08A0A024R0Q4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLD3	ENST00000409735.9 link	c.1326G>A	p.Ala442Ala	synonymous_variant	Exon 13 of 13	1	NM_012268.4	ENSP00000386938.3		Q8IV08

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

GnomAD2 exomes

AF:

0.0133

AC:

3327

AN:

250520

AF XY:

0.0133

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 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

African (AFR)

AF:

0.00433

AC:

145

AN:

33476

American (AMR)

AF:

0.0217

AC:

968

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.00107

AC:

AN:

26066

East Asian (EAS)

AF:

0.00395

AC:

157

AN:

39698

South Asian (SAS)

AF:

0.0115

AC:

988

AN:

86180

European-Finnish (FIN)

AF:

0.00846

AC:

451

AN:

53332

Middle Eastern (MID)

AF:

0.00434

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0175

AC:

19450

AN:

1111694

Other (OTH)

AF:

0.0160

AC:

963

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

1324

2648

3971

5295

6619

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

742

1484

2226

2968

3710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0132

AC:

2003

AN:

152238

Hom.:

Cov.:

AF XY:

0.0135

AC XY:

1004

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.00505

AC:

210

AN:

41552

American (AMR)

AF:

0.0267

AC:

408

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3470

East Asian (EAS)

AF:

0.00425

AC:

AN:

5178

South Asian (SAS)

AF:

0.0110

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00960

AC:

102

AN:

10624

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0172

AC:

1170

AN:

67986

Other (OTH)

AF:

0.00757

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

198

298

397

496

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0123

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PLD3: BP4, BP7, BS1, BS2 -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

DANN

Benign

0.80

PhyloP100

-3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over