chr14-104927219-G-C

Position:

• chr14-104927219-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138790.5(PLD4):​c.79G>C​(p.Glu27Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 1,549,494 control chromosomes in the GnomAD database, including 164,635 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.41 (13878 hom., cov: 33)
  • Exomes 𝑓: 0.46 (150757 hom.)
• Consequence: PLD4 NM_138790.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.7715872E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLD4	NM_138790.5	c.79G>C	p.Glu27Gln	missense_variant	2/11	ENST00000392593.9
PLD4	NM_001308174.2	c.100G>C	p.Glu34Gln	missense_variant	2/11
PLD4	XM_011536411.3	c.100G>C	p.Glu34Gln	missense_variant	2/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLD4	ENST00000392593.9	c.79G>C	p.Glu27Gln	missense_variant	2/11	1	NM_138790.5	P2

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62705 AN: 152028 Hom.: 13875 Cov.: 33

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.407

GnomAD3 exomes AF: 0.449 AC: 69774 AN: 155536 Hom.: 16486 AF XY: 0.443 AC XY: 37085 AN XY: 83732

Gnomad AFR exome AF: 0.229

Gnomad AMR exome AF: 0.500

Gnomad ASJ exome AF: 0.340

Gnomad EAS exome AF: 0.566

Gnomad SAS exome AF: 0.382

Gnomad FIN exome AF: 0.592

Gnomad NFE exome AF: 0.444

Gnomad OTH exome AF: 0.411

GnomAD4 exome AF: 0.460 AC: 642751 AN: 1397348 Hom.: 150757 Cov.: 37 AF XY: 0.457 AC XY: 315397 AN XY: 689726

Gnomad4 AFR exome AF: 0.240

Gnomad4 AMR exome AF: 0.493

Gnomad4 ASJ exome AF: 0.345

Gnomad4 EAS exome AF: 0.602

Gnomad4 SAS exome AF: 0.387

Gnomad4 FIN exome AF: 0.594

Gnomad4 NFE exome AF: 0.465

Gnomad4 OTH exome AF: 0.432

GnomAD4 genome AF: 0.412 AC: 62731 AN: 152146 Hom.: 13878 Cov.: 33 AF XY: 0.417 AC XY: 31037 AN XY: 74366

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.435

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.577

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.595

Gnomad4 NFE AF: 0.468

Gnomad4 OTH AF: 0.407

Alfa AF: 0.438 Hom.: 4882

Bravo AF: 0.396

TwinsUK AF: 0.456 AC: 1690

ALSPAC AF: 0.458 AC: 1765

ESP6500AA AF: 0.223 AC: 832

ESP6500EA AF: 0.442 AC: 3591

ExAC AF: 0.343 AC: 36709

Asia WGS AF: 0.428 AC: 1487 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.3
DANN	Benign	0.29
DEOGEN2	Benign	0.0077	.;T;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.37	T;T;T;T
MetaRNN	Benign	0.000038	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.95	.;.;L;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.41	.;N;N;N
REVEL	Benign	0.024
Sift	Benign	0.52	.;T;T;T
Sift4G	Benign	0.56	.;T;T;T
Polyphen		0.15, 0.092	.;B;B;.
Vest4		0.023, 0.050
MPC		0.084
ClinPred		0.0036	T
GERP RS		1.2
Varity_R		0.079
gMVP		0.25

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

Other links and lift over

dbSNP: rs2841280; hg19: chr14-105393556; COSMIC: COSV66914707; COSMIC: COSV66914707;