chr20-45899640-C-G

Variant names:

• chr20-45899640-C-G
• rs145642115
• NM_006227.4:c.1264G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006227.4(PLTP):​c.1264G>C​(p.Val422Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V422M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLTP NM_006227.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.80
• Publications: 6 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30990922).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006227.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLTP	NM_006227.4	MANE Select	c.1264G>C	p.Val422Leu	missense	Exon 14 of 16	NP_006218.1	P55058-1
	PLTP	NM_182676.3		c.1108G>C	p.Val370Leu	missense	Exon 13 of 15	NP_872617.1	P55058-2
	PLTP	NM_001242921.1		c.1000G>C	p.Val334Leu	missense	Exon 12 of 14	NP_001229850.1	P55058-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLTP	ENST00000372431.8	TSL:1 MANE Select	c.1264G>C	p.Val422Leu	missense	Exon 14 of 16	ENSP00000361508.3	P55058-1
	PLTP	ENST00000477313.5	TSL:1	c.1264G>C	p.Val422Leu	missense	Exon 13 of 15	ENSP00000417138.1	P55058-1
	PLTP	ENST00000354050.8	TSL:1	c.1108G>C	p.Val370Leu	missense	Exon 13 of 15	ENSP00000335290.4	P55058-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	0.0054	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	2.0	M
PhyloP100		2.8
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.14
Sift	Benign	0.12	T
Sift4G	Uncertain	0.021	D
Polyphen		0.96	D
Vest4		0.46
MVP		0.49
MPC		0.52
ClinPred		0.92	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.26
gMVP		0.60
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs145642115; hg19: chr20-44528279;