chr19-40366834-C-G

Variant summary

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

The NM_012268.4(PLD3):​c.164C>G​(p.Thr55Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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. T55I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

PLD3
NM_012268.4 missense

Scores

1
2
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.00
Variant links:
Genes affected
PLD3 (HGNC:17158): (phospholipase D family member 3) This gene encodes a member of the phospholipase D (PLD) family of enzymes that catalyze the hydrolysis of membrane phospholipids. The encoded protein is a single-pass type II membrane protein and contains two PLD phosphodiesterase domains. This protein influences processing of amyloid-beta precursor protein. Mutations in this gene are associated with Alzheimer disease risk. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Apr 2014]

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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=0.19043079).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PLD3NM_012268.4 linkc.164C>G p.Thr55Ser missense_variant Exon 5 of 13 ENST00000409735.9 NP_036400.2 Q8IV08A0A024R0Q4
PLD3NM_001031696.4 linkc.164C>G p.Thr55Ser missense_variant Exon 5 of 13 NP_001026866.1 Q8IV08A0A024R0Q4
PLD3NM_001291311.2 linkc.164C>G p.Thr55Ser missense_variant Exon 5 of 13 NP_001278240.1 Q8IV08A0A024R0Q4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PLD3ENST00000409735.9 linkc.164C>G p.Thr55Ser missense_variant Exon 5 of 13 1 NM_012268.4 ENSP00000386938.3 Q8IV08

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.094
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
21
DANN
Benign
0.97
DEOGEN2
Benign
0.017
.;T;T;T;T;T;T;T;.;T;T
Eigen
Benign
-0.013
Eigen_PC
Benign
0.20
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Benign
0.67
T;T;.;.;T;.;.;T;T;T;T
M_CAP
Benign
0.0087
T
MetaRNN
Benign
0.19
T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.98
.;.;L;L;.;L;L;.;.;L;.
PrimateAI
Uncertain
0.72
T
PROVEAN
Benign
-0.44
.;N;N;N;.;N;N;.;.;N;N
REVEL
Benign
0.10
Sift
Benign
0.65
.;T;T;T;.;T;T;.;.;T;T
Sift4G
Pathogenic
0.0
D;T;T;T;D;T;T;D;T;T;T
Polyphen
0.19
.;.;B;B;.;B;B;.;.;B;.
Vest4
0.57, 0.53, 0.57, 0.53, 0.58
MutPred
0.35
Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);
MVP
0.58
MPC
0.34
ClinPred
0.43
T
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.067
gMVP
0.47

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.

Other links and lift over

dbSNP: rs977484313; hg19: chr19-40872741; API