3-171603233-C-T

Position:

chr3-171603233-C-T

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLD1	NM_002662.5 link	c.3070G>A	p.Val1024Ile	missense_variant	27/27	ENST00000351298.9	NP_002653.1	Q13393-1Q59EA4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLD1	ENST00000351298.9 link	c.3070G>A	p.Val1024Ile	missense_variant	27/27	1	NM_002662.5	ENSP00000342793.4		Q13393-1
PLD1	ENST00000356327.9 link	c.2956G>A	p.Val986Ile	missense_variant	26/26	1		ENSP00000348681.5		Q13393-2

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

GnomAD3 exomes

AF:

0.00242

AC:

607

AN:

251102

Hom.:

AF XY:

0.00216

AC XY:

293

AN XY:

135706

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 SAS exome

AF:

0.000588

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

Gnomad4 AFR exome

AF:

0.0219

Gnomad4 AMR exome

AF:

0.00228

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000649

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.00235

Gnomad4 OTH exome

AF:

0.00295

GnomAD4 genome

AF:

0.00685

AC:

1043

AN:

152264

Hom.:

Cov.:

AF XY:

0.00674

AC XY:

502

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0198

Gnomad4 AMR

AF:

0.00373

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00206

Gnomad4 OTH

AF:

0.00806

Alfa

AF:

0.00310

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

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 13, 2024	- -

PLD1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 10, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.6

DANN

Benign

0.90

DEOGEN2

Benign

0.041

.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.52

T;T

MetaRNN

Benign

0.0025

T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

-0.41

.;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.43

N;N

REVEL

Benign

0.14

Sift

Benign

0.60

T;T

Sift4G

Benign

0.28

T;T

Polyphen

0.0

.;B

Vest4

0.053

MVP

0.20

MPC

0.083

ClinPred

0.0018

GERP RS

3.7

Varity_R

0.037

gMVP

0.14

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

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