14-104929316-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_138790.5(PLD4):c.478C>G(p.Leu160Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,430,432 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PLD4 NM_138790.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.272

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]

ACMG classification

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=0.049161315).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLD4	NM_138790.5	c.478C>G	p.Leu160Val	missense_variant	5/11	ENST00000392593.9
PLD4	NM_001308174.2	c.499C>G	p.Leu167Val	missense_variant	5/11
PLD4	XM_011536411.3	c.499C>G	p.Leu167Val	missense_variant	5/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLD4	ENST00000392593.9	c.478C>G	p.Leu160Val	missense_variant	5/11	1	NM_138790.5	P2
PLD4	ENST00000540372.5	c.499C>G	p.Leu167Val	missense_variant	5/11	2		A2
PLD4	ENST00000649344.1	c.478C>G	p.Leu160Val	missense_variant	5/11
PLD4	ENST00000557573.1	c.472C>G	p.Leu158Val	missense_variant	5/7	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1430432 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 708538

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000182

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2021

The c.478C>G (p.L160V) alteration is located in exon 5 (coding exon 4) of the PLD4 gene. This alteration results from a C to G substitution at nucleotide position 478, causing the leucine (L) at amino acid position 160 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	0.079
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
Cadd	Benign	12
Dann	Benign	0.87
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.61	T;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.049	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.46	T
Polyphen		0.0030, 0.0020	.;B;B;.
Vest4		0.28, 0.28
MutPred		0.53		.;Gain of catalytic residue at Q162 (P = 0.1227);.;.;
MVP		0.072
MPC		0.092
ClinPred		0.065	T
GERP RS		0.86
Varity_R		0.044
gMVP		0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-105395653;