dbSNP rs4490097: PLD3:c.-279+7049A>C (chr19-40355817-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012268.4(PLD3):c.-279+7049A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 151,784 control chromosomes in the GnomAD database, including 12,131 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 0.37 ( 12126 hom., cov: 29)

Exomes 𝑓: 0.58 ( 5 hom. )

Consequence

PLD3
NM_012268.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.368

Publications

13 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:

ENSG00000279759 (HGNC:):

ENSG00000279759 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLD3	NM_012268.4 link	c.-279+7049A>C		intron_variant	Intron 1 of 12	ENST00000409735.9	NP_036400.2
PLD3	NM_001031696.4 link	c.-99+7093A>C		intron_variant	Intron 1 of 12		NP_001026866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLD3	ENST00000409735.9 link	c.-279+7049A>C		intron_variant	Intron 1 of 12	1	NM_012268.4	ENSP00000386938.3

Frequencies

GnomAD3 genomes

AF:

0.374

AC:

56655

AN:

151640

Hom.:

12129

Cov.:

show subpopulations

Gnomad AFR

AF:

0.156

Gnomad AMI

AF:

0.301

Gnomad AMR

AF:

0.496

Gnomad ASJ

AF:

0.381

Gnomad EAS

AF:

0.493

Gnomad SAS

AF:

0.619

Gnomad FIN

AF:

0.379

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.451

Gnomad OTH

AF:

0.395

GnomAD4 exome

AF:

0.577

AC:

AN:

Hom.:

Cov.:

AF XY:

0.545

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.750

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.611

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.595

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<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:

0.373

AC:

56661

AN:

151758

Hom.:

12126

Cov.:

AF XY:

0.375

AC XY:

27805

AN XY:

74114

show subpopulations

African (AFR)

AF:

0.155

AC:

6439

AN:

41464

American (AMR)

AF:

0.496

AC:

7539

AN:

15196

Ashkenazi Jewish (ASJ)

AF:

0.381

AC:

1323

AN:

3470

East Asian (EAS)

AF:

0.493

AC:

2536

AN:

5142

South Asian (SAS)

AF:

0.619

AC:

2975

AN:

4808

European-Finnish (FIN)

AF:

0.379

AC:

3984

AN:

10506

Middle Eastern (MID)

AF:

0.405

AC:

119

AN:

294

European-Non Finnish (NFE)

AF:

0.451

AC:

30637

AN:

67858

Other (OTH)

AF:

0.396

AC:

835

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1667

3333

5000

6666

8333

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

560

1120

1680

2240

2800

<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:

0.419

Hom.:

18095

Bravo

AF:

0.371

Asia WGS

AF:

0.529

AC:

1837

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

3.2

(source)

DANN

Benign

0.70

PhyloP100

0.37

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over