3-171603233-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002662.5(PLD1):c.3070G>A(p.Val1024Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00294 in 1,613,990 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0068 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 18 hom. )

Consequence

PLD1
NM_002662.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.37

Publications

8 publications found

Variant links:

Genes affected

PLD1 (HGNC:9067): (phospholipase D1) This gene encodes a phosphatidylcholine-specific phospholipase which catalyzes the hydrolysis of phosphatidylcholine in order to yield phosphatidic acid and choline. The enzyme may play a role in signal transduction and subcellular trafficking. Alternative splicing results in multiple transcript variants with both catalytic and regulatory properties. [provided by RefSeq, Sep 2011]

PLD1 Gene-Disease associations (from GenCC):

cardiac valvular defect, developmental
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
PLD1-related congenital heart disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

PLD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025039613).

BP6

Variant 3-171603233-C-T is Benign according to our data. Variant chr3-171603233-C-T is described in ClinVar as Benign. ClinVar VariationId is 708886.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00685 (1043/152264) while in subpopulation AFR AF = 0.0198 (824/41570). AF 95% confidence interval is 0.0187. There are 10 homozygotes in GnomAd4. There are 502 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002662.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLD1	NM_002662.5	MANE Select	c.3070G>A	p.Val1024Ile	missense	Exon 27 of 27	NP_002653.1	Q13393-1
	PLD1	NM_001130081.3		c.2956G>A	p.Val986Ile	missense	Exon 26 of 26	NP_001123553.1	Q13393-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLD1	ENST00000351298.9	TSL:1 MANE Select	c.3070G>A	p.Val1024Ile	missense	Exon 27 of 27	ENSP00000342793.4	Q13393-1
PLD1	ENST00000356327.9	TSL:1	c.2956G>A	p.Val986Ile	missense	Exon 26 of 26	ENSP00000348681.5	Q13393-2
PLD1	ENST00000959555.1		c.3070G>A	p.Val1024Ile	missense	Exon 27 of 27	ENSP00000629614.1

Frequencies

GnomAD3 genomes

AF:

0.00681

AC:

1036

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0197

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00206

Gnomad OTH

AF:

0.00815

GnomAD2 exomes

AF:

0.00242

AC:

607

AN:

251102

AF XY:

0.00216

show subpopulations

Gnomad AFR exome

AF:

0.0187

Gnomad AMR exome

AF:

0.00197

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00181

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00253

AC:

3705

AN:

1461726

Hom.:

Cov.:

AF XY:

0.00240

AC XY:

1742

AN XY:

727168

show subpopulations

African (AFR)

AF:

0.0219

AC:

732

AN:

33476

American (AMR)

AF:

0.00228

AC:

102

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39690

South Asian (SAS)

AF:

0.000649

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00399

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00235

AC:

2611

AN:

1111914

Other (OTH)

AF:

0.00295

AC:

178

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

185

370

556

741

926

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

228

342

456

570

<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:

0.00685

AC:

1043

AN:

152264

Hom.:

Cov.:

AF XY:

0.00674

AC XY:

502

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0198

AC:

824

AN:

41570

American (AMR)

AF:

0.00373

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000830

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00206

AC:

140

AN:

68016

Other (OTH)

AF:

0.00806

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

106

160

213

266

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00388

Hom.:

Bravo

AF:

0.00773

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.0193

AC:

ESP6500EA

AF:

0.00209

AC:

ExAC

AF:

0.00268

AC:

326

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00240

EpiControl

AF:

0.00231

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

PLD1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.6

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.041

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.52

MetaRNN

Benign

0.0025

MetaSVM

Benign

-0.84

MutationAssessor

Benign

-0.41

PhyloP100

1.4

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.43

REVEL

Benign

0.14

Sift

Benign

0.60

Sift4G

Benign

0.28

Polyphen

0.0

Vest4

0.053

MVP

0.20

MPC

0.083

ClinPred

0.0018

GERP RS

3.7

Varity_R

0.037

gMVP

0.14

Mutation Taster

=96/4

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over