Variant chr19-40366834-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_012268.4(PLD3):c.164C>T(p.Thr55Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,613,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PLD3
NM_012268.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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]

PLD3 links:

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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=0.21754283).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PLD3	NM_012268.4 linkuse as main transcript	c.164C>T	p.Thr55Ile	missense_variant	5/13	ENST00000409735.9	NP_036400.2
PLD3	NM_001031696.4 linkuse as main transcript	c.164C>T	p.Thr55Ile	missense_variant	5/13		NP_001026866.1
PLD3	NM_001291311.2 linkuse as main transcript	c.164C>T	p.Thr55Ile	missense_variant	5/13		NP_001278240.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLD3	ENST00000409735.9 linkuse as main transcript	c.164C>T	p.Thr55Ile	missense_variant	5/13	1	NM_012268.4	ENSP00000386938	P1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461770

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727182

show subpopulations

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152110

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Jun 11, 2021

The c.164C>T (p.T55I) alteration is located in exon 5 (coding exon 3) of the PLD3 gene. This alteration results from a C to T substitution at nucleotide position 164, causing the threonine (T) at amino acid position 55 to be replaced by an isoleucine (I). 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

0.21

BayesDel_addAF

Uncertain

0.097

BayesDel_noAF

Benign

-0.10

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.018

.;T;T;T;T;T;T;T;.;T;T

Eigen

Benign

-0.041

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.79

T;T;.;.;T;.;.;T;T;T;T

M_CAP

Benign

0.0091

MetaRNN

Benign

0.22

T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.90

.;.;L;L;.;L;L;.;.;L;.

MutationTaster

Benign

0.80

D;D;D;D;D

PrimateAI

Uncertain

0.79

PROVEAN

Benign

0.10

.;N;N;N;.;N;N;.;.;N;N

REVEL

Benign

0.11

Sift

Benign

0.20

.;T;T;T;.;T;T;.;.;T;T

Sift4G

Pathogenic

0.0

D;T;T;T;D;T;T;D;T;T;T

Polyphen

0.033

.;.;B;B;.;B;B;.;.;B;.

Vest4

0.85, 0.84, 0.85, 0.84, 0.85

MutPred

0.40

Loss of catalytic residue at T55 (P = 0.0519);Loss of catalytic residue at T55 (P = 0.0519);Loss of catalytic residue at T55 (P = 0.0519);Loss of catalytic residue at T55 (P = 0.0519);Loss of catalytic residue at T55 (P = 0.0519);Loss of catalytic residue at T55 (P = 0.0519);Loss of catalytic residue at T55 (P = 0.0519);Loss of catalytic residue at T55 (P = 0.0519);Loss of catalytic residue at T55 (P = 0.0519);Loss of catalytic residue at T55 (P = 0.0519);Loss of catalytic residue at T55 (P = 0.0519);

MVP

0.61

MPC

0.41

ClinPred

0.43

GERP RS

5.7

Varity_R

0.065

gMVP

0.50

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

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