chr20-45899081-G-C

Variant names:

• chr20-45899081-G-C
• NM_006227.4:c.1360-18C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_006227.4(PLTP):​c.1360-18C>G variant causes a intron 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 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.135
• 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]

CTSA (HGNC:9251): (cathepsin A) This gene encodes a member of the peptidase S10 family of serine carboxypeptidases. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate two chains that comprise the heterodimeric active enzyme. This enzyme possesses deamidase, esterase and carboxypeptidase activities and acts as a scaffold in the lysosomal multienzyme complex. Mutations in this gene are associated with galactosialidosis. [provided by RefSeq, Nov 2015]

CTSA Gene-Disease associations (from GenCC):

• galactosialidosis

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, ClinGen, Illumina

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 20-45899081-G-C is Benign according to our data. Variant chr20-45899081-G-C is described in CliVar as Likely_benign. Clinvar id is 2996548.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-45899081-G-C is described in CliVar as Likely_benign. Clinvar id is 2996548.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-45899081-G-C is described in CliVar as Likely_benign. Clinvar id is 2996548.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-45899081-G-C is described in CliVar as Likely_benign. Clinvar id is 2996548.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-45899081-G-C is described in CliVar as Likely_benign. Clinvar id is 2996548.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-45899081-G-C is described in CliVar as Likely_benign. Clinvar id is 2996548.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-45899081-G-C is described in CliVar as Likely_benign. Clinvar id is 2996548.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-45899081-G-C is described in CliVar as Likely_benign. Clinvar id is 2996548.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-45899081-G-C is described in CliVar as Likely_benign. Clinvar id is 2996548.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-45899081-G-C is described in CliVar as Likely_benign. Clinvar id is 2996548.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-45899081-G-C is described in CliVar as Likely_benign. Clinvar id is 2996548.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-45899081-G-C is described in CliVar as Likely_benign. Clinvar id is 2996548.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-45899081-G-C is described in CliVar as Likely_benign. Clinvar id is 2996548.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-45899081-G-C is described in CliVar as Likely_benign. Clinvar id is 2996548.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-45899081-G-C is described in CliVar as Likely_benign. Clinvar id is 2996548.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-45899081-G-C is described in CliVar as Likely_benign. Clinvar id is 2996548.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-45899081-G-C is described in CliVar as Likely_benign. Clinvar id is 2996548.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-45899081-G-C is described in CliVar as Likely_benign. Clinvar id is 2996548.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-45899081-G-C is described in CliVar as Likely_benign. Clinvar id is 2996548.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-45899081-G-C is described in CliVar as Likely_benign. Clinvar id is 2996548.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-45899081-G-C is described in CliVar as Likely_benign. Clinvar id is 2996548.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-45899081-G-C is described in CliVar as Likely_benign. Clinvar id is 2996548.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-45899081-G-C is described in CliVar as Likely_benign. Clinvar id is 2996548.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-45899081-G-C is described in CliVar as Likely_benign. Clinvar id is 2996548.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-45899081-G-C is described in CliVar as Likely_benign. Clinvar id is 2996548.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-45899081-G-C is described in CliVar as Likely_benign. Clinvar id is 2996548.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-45899081-G-C is described in CliVar as Likely_benign. Clinvar id is 2996548.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-45899081-G-C is described in CliVar as Likely_benign. Clinvar id is 2996548.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLTP	NM_006227.4	c.1360-18C>G		intron_variant	Intron 15 of 15	ENST00000372431.8	NP_006218.1
PLTP	NM_182676.3	c.1204-18C>G		intron_variant	Intron 14 of 14		NP_872617.1
PLTP	NM_001242921.1	c.1096-18C>G		intron_variant	Intron 13 of 13		NP_001229850.1
PLTP	NM_001242920.2	c.1075-18C>G		intron_variant	Intron 13 of 13		NP_001229849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLTP	ENST00000372431.8	c.1360-18C>G		intron_variant	Intron 15 of 15	1	NM_006227.4	ENSP00000361508.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 18, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.97
DANN	Benign	0.63
PhyloP100		-0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr20-44527720;