Variant chr14-104928790-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_138790.5(PLD4):c.326C>T(p.Ala109Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000028 in 1,606,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

PLD4
NM_138790.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.163

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:

PLD4 (HGNC:):

PLD4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.027372211).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLD4	NM_138790.5 linkuse as main transcript	c.326C>T	p.Ala109Val	missense_variant	4/11	ENST00000392593.9	NP_620145.2	Q96BZ4B4DI07B4DJQ6
PLD4	NM_001308174.2 linkuse as main transcript	c.347C>T	p.Ala116Val	missense_variant	4/11		NP_001295103.1	B4DI07B4DJQ6F5H2B5
PLD4	XM_011536411.3 linkuse as main transcript	c.347C>T	p.Ala116Val	missense_variant	4/11		XP_011534713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLD4	ENST00000392593.9 linkuse as main transcript	c.326C>T	p.Ala109Val	missense_variant	4/11	1	NM_138790.5	ENSP00000376372.5		Q96BZ4

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000531

AC:

AN:

244900

Hom.:

AF XY:

0.0000374

AC XY:

AN XY:

133626

show subpopulations

Gnomad AFR exome

AF:

0.000394

Gnomad AMR exome

AF:

0.0000875

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000986

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000168

GnomAD4 exome

AF:

0.0000158

AC:

AN:

1454292

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

722298

show subpopulations

Gnomad4 AFR exome

AF:

0.000420

Gnomad4 AMR exome

AF:

0.0000450

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000698

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.03e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000144

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.000159

ESP6500AA

AF:

0.000771

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000498

AC:

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, 2024

The c.326C>T (p.A109V) alteration is located in exon 4 (coding exon 3) of the PLD4 gene. This alteration results from a C to T substitution at nucleotide position 326, causing the alanine (A) at amino acid position 109 to be replaced by a valine (V). 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

0.074

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.016

.;T;T;T

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.67

T;T;T;T

M_CAP

Benign

0.0098

MetaRNN

Benign

0.027

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.83

.;.;L;.

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.0

.;N;N;N

REVEL

Benign

0.035

Sift

Benign

0.33

.;T;T;T

Sift4G

Benign

0.33

.;T;T;T

Polyphen

0.0

.;B;B;.

Vest4

0.068

MVP

0.17

MPC

0.085

ClinPred

0.0085

GERP RS

1.3

Varity_R

0.073

gMVP

0.34

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