chr19-40366661-G-A

Position:

• chr19-40366661-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012268.4(PLD3):​c.79G>A​(p.Glu27Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLD3 NM_012268.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.08

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]

PLD3 (HGNC:):

ACMG classification

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=0.17978561).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLD3	NM_012268.4	c.79G>A	p.Glu27Lys	missense_variant	4/13	ENST00000409735.9	NP_036400.2
PLD3	NM_001031696.4	c.79G>A	p.Glu27Lys	missense_variant	4/13		NP_001026866.1
PLD3	NM_001291311.2	c.79G>A	p.Glu27Lys	missense_variant	4/13		NP_001278240.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLD3	ENST00000409735.9	c.79G>A	p.Glu27Lys	missense_variant	4/13	1	NM_012268.4	ENSP00000386938.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Mayo Clinic Laboratories, Mayo Clinic

Feb 27, 2023

BP4, PM2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.027	.;T;T;T;T;T;T;T;T;T;.;T;T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.039
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.88	D;D;D;.;.;D;.;D;.;D;D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.18	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	.;.;.;L;L;.;L;.;L;.;.;L;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.81	.;N;.;N;N;.;N;.;N;.;.;N;N
REVEL	Benign	0.19
Sift	Benign	0.16	.;T;.;T;T;.;T;.;T;.;.;T;T
Sift4G	Pathogenic	0.0	D;T;D;T;T;D;T;D;T;D;T;T;T
Polyphen		0.83	.;.;.;P;P;.;P;.;P;.;.;P;.
Vest4		0.21, 0.48, 0.21, 0.49
MutPred		0.38		Gain of MoRF binding (P = 0.0065);Gain of MoRF binding (P = 0.0065);Gain of MoRF binding (P = 0.0065);Gain of MoRF binding (P = 0.0065);Gain of MoRF binding (P = 0.0065);Gain of MoRF binding (P = 0.0065);Gain of MoRF binding (P = 0.0065);Gain of MoRF binding (P = 0.0065);Gain of MoRF binding (P = 0.0065);Gain of MoRF binding (P = 0.0065);Gain of MoRF binding (P = 0.0065);Gain of MoRF binding (P = 0.0065);Gain of MoRF binding (P = 0.0065);
MVP		0.56
MPC		0.86
ClinPred		0.84	D
GERP RS		3.4
Varity_R		0.050
gMVP		0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr19-40872568;