NM_006227.4:c.1263G>A

Variant names:

• chr20-45899641-C-T
• NM_006227.4:c.1263G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_006227.4(PLTP):​c.1263G>A​(p.Gly421Gly) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLTP NM_006227.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.56
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 20-45899641-C-T is Benign according to our data. Variant chr20-45899641-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3648414.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.56 with no splicing effect.

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.1263G>A	p.Gly421Gly	synonymous	Exon 14 of 16	NP_006218.1	P55058-1
	PLTP	NM_182676.3		c.1107G>A	p.Gly369Gly	synonymous	Exon 13 of 15	NP_872617.1	P55058-2
	PLTP	NM_001242921.1		c.999G>A	p.Gly333Gly	synonymous	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.1263G>A	p.Gly421Gly	synonymous	Exon 14 of 16	ENSP00000361508.3	P55058-1
	PLTP	ENST00000477313.5	TSL:1	c.1263G>A	p.Gly421Gly	synonymous	Exon 13 of 15	ENSP00000417138.1	P55058-1
	PLTP	ENST00000354050.8	TSL:1	c.1107G>A	p.Gly369Gly	synonymous	Exon 13 of 15	ENSP00000335290.4	P55058-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	2.2
DANN	Benign	0.76
PhyloP100		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

hg19: chr20-44528280;