dbSNP rs780085373: PLD4:p.Pro181Gln (chr14-104929380-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

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

The NM_138790.5(PLD4):c.542C>A(p.Pro181Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,408,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P181L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PLD4
NM_138790.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.680

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30172324).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLD4	NM_138790.5 link	c.542C>A	p.Pro181Gln	missense_variant	Exon 5 of 11	ENST00000392593.9	NP_620145.2	Q96BZ4B4DI07B4DJQ6
PLD4	NM_001308174.2 link	c.563C>A	p.Pro188Gln	missense_variant	Exon 5 of 11		NP_001295103.1	B4DI07B4DJQ6F5H2B5
PLD4	XM_011536411.3 link	c.563C>A	p.Pro188Gln	missense_variant	Exon 5 of 11		XP_011534713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PLD4	ENST00000392593.9 link	c.542C>A	p.Pro181Gln	missense_variant	Exon 5 of 11	1	NM_138790.5	ENSP00000376372.5	Q96BZ4
PLD4	ENST00000540372.5 link	c.563C>A	p.Pro188Gln	missense_variant	Exon 5 of 11	2		ENSP00000438677.1	F5H2B5
PLD4	ENST00000649344.1 link	c.542C>A	p.Pro181Gln	missense_variant	Exon 5 of 11			ENSP00000497627.1	A0A3B3IT68
PLD4	ENST00000557573.1 link	c.536C>A	p.Pro179Gln	missense_variant	Exon 5 of 7	3		ENSP00000451278.1	G3V3J8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000602

AC:

AN:

166248

Hom.:

AF XY:

0.00

AC XY:

AN XY:

89116

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000382

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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

AF:

0.00000142

AC:

AN:

1408756

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

695908

show subpopulations

Gnomad4 AFR exome

AF:

0.0000311

Gnomad4 AMR exome

AF:

0.0000267

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.12

.;T;T;T

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.65

T;T;T;T

M_CAP

Benign

0.062

MetaRNN

Benign

0.30

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.8

.;.;M;.

PrimateAI

Benign

0.32

PROVEAN

Pathogenic

-7.6

.;D;D;D

REVEL

Benign

0.14

Sift

Uncertain

0.0010

.;D;D;D

Sift4G

Uncertain

0.044

.;D;D;D

Polyphen

0.92, 0.87

.;P;P;.

Vest4

0.32, 0.32

MutPred

0.36

.;Loss of glycosylation at P188 (P = 0.0409);.;.;

MVP

0.27

MPC

0.44

ClinPred

0.96

GERP RS

3.3

Varity_R

0.43

gMVP

0.53

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over