Variant 20-45899538-T-G 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_006227.4(PLTP):c.1283A>C(p.Glu428Ala) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000137 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PLTP
NM_006227.4 missense, splice_region

Scores

Splicing: ADA: 0.5635

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.86

Variant links:

Genes affected

PLTP (HGNC:9093): (phospholipid transfer protein) The protein encoded by this gene is one of at least two lipid transfer proteins found in human plasma. The encoded protein transfers phospholipids from triglyceride-rich lipoproteins to high density lipoprotein (HDL). In addition to regulating the size of HDL particles, this protein may be involved in cholesterol metabolism. At least two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

PLTP 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=0.23933607).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PLTP	NM_006227.4 linkuse as main transcript	c.1283A>C	p.Glu428Ala	missense_variant, splice_region_variant	15/16	ENST00000372431.8
PLTP	NM_182676.3 linkuse as main transcript	c.1127A>C	p.Glu376Ala	missense_variant, splice_region_variant	14/15
PLTP	NM_001242921.1 linkuse as main transcript	c.1019A>C	p.Glu340Ala	missense_variant, splice_region_variant	13/14
PLTP	NM_001242920.2 linkuse as main transcript	c.998A>C	p.Glu333Ala	missense_variant, splice_region_variant	13/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLTP	ENST00000372431.8 linkuse as main transcript	c.1283A>C	p.Glu428Ala	missense_variant, splice_region_variant	15/16	1	NM_006227.4	P1	P55058-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251478

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Sep 30, 2022

The c.1283A>C (p.E428A) alteration is located in exon 15 (coding exon 14) of the PLTP gene. This alteration results from a A to C substitution at nucleotide position 1283, causing the glutamic acid (E) at amino acid position 428 to be replaced by an alanine (A). 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

0.13

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

0.10

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.91

D;D;.;D;D

M_CAP

Benign

0.010

MetaRNN

Benign

0.24

T;T;T;T;T

MetaSVM

Benign

-0.94

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.6

N;N;N;N;N

REVEL

Benign

0.12

Sift

Uncertain

0.0070

D;D;T;T;T

Sift4G

Benign

0.074

T;T;T;T;T

Polyphen

0.67

P;.;P;P;.

Vest4

0.41

MVP

0.099

MPC

0.43

ClinPred

0.56

GERP RS

4.7

Varity_R

0.30

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.56

dbscSNV1_RF

Pathogenic

0.74

SpliceAI score (max)

0.030

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

Other links and lift over