Variant chr14-104928919-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_138790.5(PLD4):c.455C>G(p.Ser152Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000756 in 1,600,274 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 1 hom., cov: 34)

Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

PLD4
NM_138790.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.04

Variant links:

Genes affected

PLD4 (HGNC:23792): (phospholipase D family member 4) Predicted to enable single-stranded DNA 5'-3' exodeoxyribonuclease activity. Predicted to be involved in hematopoietic progenitor cell differentiation; phagocytosis; and regulation of cytokine production involved in inflammatory response. Predicted to be located in early endosome and endoplasmic reticulum membrane. Predicted to be active in several cellular components, including endoplasmic reticulum; phagocytic vesicle; and trans-Golgi network membrane. [provided by Alliance of Genome Resources, Apr 2022]

PLD4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32256746).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PLD4	NM_138790.5 linkuse as main transcript	c.455C>G	p.Ser152Trp	missense_variant	4/11	ENST00000392593.9
PLD4	NM_001308174.2 linkuse as main transcript	c.476C>G	p.Ser159Trp	missense_variant	4/11
PLD4	XM_011536411.3 linkuse as main transcript	c.476C>G	p.Ser159Trp	missense_variant	4/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLD4	ENST00000392593.9 linkuse as main transcript	c.455C>G	p.Ser152Trp	missense_variant	4/11	1	NM_138790.5	P2

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000122

AC:

AN:

245376

Hom.:

AF XY:

0.000142

AC XY:

AN XY:

133604

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000879

Gnomad ASJ exome

AF:

0.000715

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000133

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000126

Gnomad OTH exome

AF:

0.000336

GnomAD4 exome

AF:

0.0000746

AC:

108

AN:

1447924

Hom.:

Cov.:

AF XY:

0.0000739

AC XY:

AN XY:

717540

show subpopulations

Gnomad4 AFR exome

AF:

0.000481

Gnomad4 AMR exome

AF:

0.0000677

Gnomad4 ASJ exome

AF:

0.000502

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000187

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000281

Gnomad4 OTH exome

AF:

0.000268

GnomAD4 genome

AF:

0.0000853

AC:

AN:

152350

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.000102

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000357

AC:

ExAC

AF:

0.000141

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000297

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2021

The c.455C>G (p.S152W) alteration is located in exon 4 (coding exon 3) of the PLD4 gene. This alteration results from a C to G substitution at nucleotide position 455, causing the serine (S) at amino acid position 152 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

.;T;T;T

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.92

D;D;D;D

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.32

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.8

.;.;M;.

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-5.0

.;D;D;D

REVEL

Benign

0.24

Sift

Uncertain

0.0040

.;D;D;D

Sift4G

Uncertain

0.013

.;D;D;D

Polyphen

0.99, 0.98

.;D;D;.

Vest4

0.57, 0.60

MVP

0.42

MPC

0.54

ClinPred

0.81

GERP RS

4.2

Varity_R

0.40

gMVP

0.73

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