Variant 14-104929312-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138790.5(PLD4):c.474G>C(p.Glu158Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

PLD4
NM_138790.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.09

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20489526).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PLD4	NM_138790.5 linkuse as main transcript	c.474G>C	p.Glu158Asp	missense_variant	5/11	ENST00000392593.9
PLD4	NM_001308174.2 linkuse as main transcript	c.495G>C	p.Glu165Asp	missense_variant	5/11
PLD4	XM_011536411.3 linkuse as main transcript	c.495G>C	p.Glu165Asp	missense_variant	5/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PLD4	ENST00000392593.9 linkuse as main transcript	c.474G>C	p.Glu158Asp	missense_variant	5/11	1	NM_138790.5	P2
PLD4	ENST00000540372.5 linkuse as main transcript	c.495G>C	p.Glu165Asp	missense_variant	5/11	2		A2
PLD4	ENST00000649344.1 linkuse as main transcript	c.474G>C	p.Glu158Asp	missense_variant	5/11
PLD4	ENST00000557573.1 linkuse as main transcript	c.468G>C	p.Glu156Asp	missense_variant	5/7	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000511

AC:

AN:

195570

Hom.:

AF XY:

0.00

AC XY:

AN XY:

105968

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000678

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Jun 29, 2023

The c.474G>C (p.E158D) alteration is located in exon 5 (coding exon 4) of the PLD4 gene. This alteration results from a G to C substitution at nucleotide position 474, causing the glutamic acid (E) at amino acid position 158 to be replaced by an aspartic acid (D). 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

0.29

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.077

.;T;T;T

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.75

T;T;T;T

M_CAP

Benign

0.0087

MetaRNN

Benign

0.20

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

.;.;M;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-2.8

.;D;D;D

REVEL

Benign

0.036

Sift

Uncertain

0.027

.;D;D;D

Sift4G

Uncertain

0.0070

.;D;D;D

Polyphen

0.36, 0.24

.;B;B;.

Vest4

0.28, 0.28

MutPred

0.32

.;Gain of catalytic residue at Q162 (P = 0.1251);.;.;

MVP

0.39

MPC

0.44

ClinPred

0.47

GERP RS

1.9

Varity_R

0.24

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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