20-45899640-C-T
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_006227.4(PLTP):c.1264G>A(p.Val422Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000263 in 1,613,896 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00029 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00026 ( 3 hom. )
Consequence
PLTP
NM_006227.4 missense
NM_006227.4 missense
Scores
8
9
Clinical Significance
Conservation
PhyloP100: 2.80
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.01150468).
BS2
High Homozygotes in GnomAdExome4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLTP | NM_006227.4 | c.1264G>A | p.Val422Met | missense_variant | 14/16 | ENST00000372431.8 | |
PLTP | NM_182676.3 | c.1108G>A | p.Val370Met | missense_variant | 13/15 | ||
PLTP | NM_001242921.1 | c.1000G>A | p.Val334Met | missense_variant | 12/14 | ||
PLTP | NM_001242920.2 | c.979G>A | p.Val327Met | missense_variant | 12/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLTP | ENST00000372431.8 | c.1264G>A | p.Val422Met | missense_variant | 14/16 | 1 | NM_006227.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000289 AC: 44AN: 152008Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000445 AC: 112AN: 251450Hom.: 1 AF XY: 0.000464 AC XY: 63AN XY: 135904
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GnomAD4 exome AF: 0.000261 AC: 381AN: 1461888Hom.: 3 Cov.: 34 AF XY: 0.000267 AC XY: 194AN XY: 727248
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GnomAD4 genome AF: 0.000289 AC: 44AN: 152008Hom.: 0 Cov.: 32 AF XY: 0.000296 AC XY: 22AN XY: 74248
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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 | Dec 22, 2023 | The c.1264G>A (p.V422M) alteration is located in exon 14 (coding exon 13) of the PLTP gene. This alteration results from a G to A substitution at nucleotide position 1264, causing the valine (V) at amino acid position 422 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D
Polyphen
D;.;D;D;.
Vest4
MVP
MPC
0.72
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at