NM_000430.4:c.1024_1031delCGTGGAGT

Variant names:

• chr17-2680184-ACGTGGAGT-A
• rs587784237
• NM_000430.4:c.1024_1031delCGTGGAGT

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_000430.4(PAFAH1B1):​c.1024_1031delCGTGGAGT​(p.Arg342SerfsTer14) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PAFAH1B1 NM_000430.4 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 9.99
• Publications: 2 publications found

Genes affected

PAFAH1B1 (HGNC:8574): (platelet activating factor acetylhydrolase 1b regulatory subunit 1) This locus was identified as encoding a gene that when mutated or lost caused the lissencephaly associated with Miller-Dieker lissencephaly syndrome. This gene encodes the non-catalytic alpha subunit of the intracellular Ib isoform of platelet-activating factor acteylhydrolase, a heterotrimeric enzyme that specifically catalyzes the removal of the acetyl group at the SN-2 position of platelet-activating factor (identified as 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine). Two other isoforms of intracellular platelet-activating factor acetylhydrolase exist: one composed of multiple subunits, the other, a single subunit. In addition, a single-subunit isoform of this enzyme is found in serum. [provided by RefSeq, Apr 2009]

PAFAH1B1 Gene-Disease associations (from GenCC):

• lissencephaly due to LIS1 mutation

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-2680184-ACGTGGAGT-A is Pathogenic according to our data. Variant chr17-2680184-ACGTGGAGT-A is described in CliVar as Pathogenic. Clinvar id is 159490.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-2680184-ACGTGGAGT-A is described in CliVar as Pathogenic. Clinvar id is 159490.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-2680184-ACGTGGAGT-A is described in CliVar as Pathogenic. Clinvar id is 159490.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-2680184-ACGTGGAGT-A is described in CliVar as Pathogenic. Clinvar id is 159490.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-2680184-ACGTGGAGT-A is described in CliVar as Pathogenic. Clinvar id is 159490.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-2680184-ACGTGGAGT-A is described in CliVar as Pathogenic. Clinvar id is 159490.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-2680184-ACGTGGAGT-A is described in CliVar as Pathogenic. Clinvar id is 159490.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-2680184-ACGTGGAGT-A is described in CliVar as Pathogenic. Clinvar id is 159490.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-2680184-ACGTGGAGT-A is described in CliVar as Pathogenic. Clinvar id is 159490.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-2680184-ACGTGGAGT-A is described in CliVar as Pathogenic. Clinvar id is 159490.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-2680184-ACGTGGAGT-A is described in CliVar as Pathogenic. Clinvar id is 159490.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-2680184-ACGTGGAGT-A is described in CliVar as Pathogenic. Clinvar id is 159490.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-2680184-ACGTGGAGT-A is described in CliVar as Pathogenic. Clinvar id is 159490.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-2680184-ACGTGGAGT-A is described in CliVar as Pathogenic. Clinvar id is 159490.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-2680184-ACGTGGAGT-A is described in CliVar as Pathogenic. Clinvar id is 159490.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-2680184-ACGTGGAGT-A is described in CliVar as Pathogenic. Clinvar id is 159490.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-2680184-ACGTGGAGT-A is described in CliVar as Pathogenic. Clinvar id is 159490.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-2680184-ACGTGGAGT-A is described in CliVar as Pathogenic. Clinvar id is 159490.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-2680184-ACGTGGAGT-A is described in CliVar as Pathogenic. Clinvar id is 159490.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-2680184-ACGTGGAGT-A is described in CliVar as Pathogenic. Clinvar id is 159490.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-2680184-ACGTGGAGT-A is described in CliVar as Pathogenic. Clinvar id is 159490.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-2680184-ACGTGGAGT-A is described in CliVar as Pathogenic. Clinvar id is 159490.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-2680184-ACGTGGAGT-A is described in CliVar as Pathogenic. Clinvar id is 159490.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-2680184-ACGTGGAGT-A is described in CliVar as Pathogenic. Clinvar id is 159490.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-2680184-ACGTGGAGT-A is described in CliVar as Pathogenic. Clinvar id is 159490.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-2680184-ACGTGGAGT-A is described in CliVar as Pathogenic. Clinvar id is 159490.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-2680184-ACGTGGAGT-A is described in CliVar as Pathogenic. Clinvar id is 159490.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-2680184-ACGTGGAGT-A is described in CliVar as Pathogenic. Clinvar id is 159490.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-2680184-ACGTGGAGT-A is described in CliVar as Pathogenic. Clinvar id is 159490.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-2680184-ACGTGGAGT-A is described in CliVar as Pathogenic. Clinvar id is 159490.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-2680184-ACGTGGAGT-A is described in CliVar as Pathogenic. Clinvar id is 159490.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-2680184-ACGTGGAGT-A is described in CliVar as Pathogenic. Clinvar id is 159490.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAFAH1B1	NM_000430.4	c.1024_1031delCGTGGAGT	p.Arg342SerfsTer14	frameshift_variant	Exon 10 of 11	ENST00000397195.10	NP_000421.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAFAH1B1	ENST00000397195.10	c.1024_1031delCGTGGAGT	p.Arg342SerfsTer14	frameshift_variant	Exon 10 of 11	1	NM_000430.4	ENSP00000380378.4

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Lissencephaly due to LIS1 mutation Pathogenic:1

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		10
Mutation Taster		=1/199	disease causing (ClinVar)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs587784237; hg19: chr17-2583478;