Variant 20-45899645-A-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 ENST00000372431.8(PLTP):c.1259T>C(p.Ile420Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

PLTP
ENST00000372431.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.63

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:

Genome browser will be placed here

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=0.18034157).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PLTP	NM_006227.4 linkuse as main transcript	c.1259T>C	p.Ile420Thr	missense_variant	14/16	ENST00000372431.8	NP_006218.1
PLTP	NM_182676.3 linkuse as main transcript	c.1103T>C	p.Ile368Thr	missense_variant	13/15		NP_872617.1
PLTP	NM_001242921.1 linkuse as main transcript	c.995T>C	p.Ile332Thr	missense_variant	12/14		NP_001229850.1
PLTP	NM_001242920.2 linkuse as main transcript	c.974T>C	p.Ile325Thr	missense_variant	12/14		NP_001229849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLTP	ENST00000372431.8 linkuse as main transcript	c.1259T>C	p.Ile420Thr	missense_variant	14/16	1	NM_006227.4	ENSP00000361508	P1	P55058-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251454

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727248

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:

0.00000899

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 provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 23, 2022

This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 420 of the PLTP protein (p.Ile420Thr). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with PLTP-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.092

.;.;T;T;.

Eigen

Benign

0.0054

Eigen_PC

Benign

0.039

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.94

D;D;.;D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.18

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.7

.;.;L;L;.

MutationTaster

Benign

0.92

D;D;D;D;D;D

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.070

N;N;N;N;N

REVEL

Benign

0.19

Sift

Benign

0.67

T;T;D;D;T

Sift4G

Uncertain

0.010

D;D;D;D;D

Polyphen

0.35

B;.;P;P;.

Vest4

0.37

MVP

0.32

MPC

0.42

ClinPred

0.57

GERP RS

4.7

Varity_R

0.17

gMVP

0.35

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

Other links and lift over