14-104930092-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_138790.5(PLD4):c.704G>A(p.Arg235Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,613,360 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000029 ( 1 hom. )
Consequence
PLD4
NM_138790.5 missense
NM_138790.5 missense
Scores
4
3
6
Clinical Significance
Conservation
PhyloP100: 7.93
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLD4 | NM_138790.5 | c.704G>A | p.Arg235Gln | missense_variant | 6/11 | ENST00000392593.9 | |
PLD4 | NM_001308174.2 | c.725G>A | p.Arg242Gln | missense_variant | 6/11 | ||
PLD4 | XM_011536411.3 | c.725G>A | p.Arg242Gln | missense_variant | 6/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLD4 | ENST00000392593.9 | c.704G>A | p.Arg235Gln | missense_variant | 6/11 | 1 | NM_138790.5 | P2 | |
PLD4 | ENST00000540372.5 | c.725G>A | p.Arg242Gln | missense_variant | 6/11 | 2 | A2 | ||
PLD4 | ENST00000649344.1 | c.704G>A | p.Arg235Gln | missense_variant | 6/11 | ||||
PLD4 | ENST00000557573.1 | c.698G>A | p.Arg233Gln | missense_variant | 6/7 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152212Hom.: 0 Cov.: 33
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000564 AC: 14AN: 248300Hom.: 0 AF XY: 0.0000592 AC XY: 8AN XY: 135064
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GnomAD4 exome AF: 0.0000294 AC: 43AN: 1461030Hom.: 1 Cov.: 31 AF XY: 0.0000358 AC XY: 26AN XY: 726828
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152330Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74484
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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 09, 2021 | The c.704G>A (p.R235Q) alteration is located in exon 6 (coding exon 5) of the PLD4 gene. This alteration results from a G to A substitution at nucleotide position 704, causing the arginine (R) at amino acid position 235 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Pathogenic
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D
PrimateAI
Benign
T
Polyphen
1.0
.;D;D;.
Vest4
0.82, 0.83
MutPred
0.72
.;Gain of catalytic residue at A237 (P = 0.0245);.;.;
MVP
0.48
MPC
0.50
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at