1-231241401-ACT-A

Position:

• chr1-231241401-ACT-A

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_014236.4(GNPAT):​c.26_27del​(p.Ser9LeufsTer25) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GNPAT NM_014236.4 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 1.16

Genes affected

GNPAT (HGNC:4416): (glyceronephosphate O-acyltransferase) This gene encodes an enzyme located in the peroxisomal membrane which is essential to the synthesis of ether phospholipids. Mutations in this gene are associated with rhizomelic chondrodysplasia punctata. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

ACMG classification

Verdict is Pathogenic. Variant got 12 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 26 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-231241401-ACT-A is Pathogenic according to our data. Variant chr1-231241401-ACT-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2675931.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNPAT	NM_014236.4	c.26_27del	p.Ser9LeufsTer25	frameshift_variant	1/16	ENST00000366647.9
GNPAT	NM_001316350.2	c.26_27del	p.Ser9LeufsTer35	frameshift_variant	1/15
GNPAT	XM_005273313.5	c.26_27del	p.Ser9LeufsTer24	frameshift_variant	1/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNPAT	ENST00000366647.9	c.26_27del	p.Ser9LeufsTer25	frameshift_variant	1/16	1	NM_014236.4	P1
GNPAT	ENST00000416000.1	c.26_27del	p.Ser9LeufsTer25	frameshift_variant	1/13	5
GNPAT	ENST00000436239.5	c.26_27del	p.Ser9LeufsTer35	frameshift_variant	1/6	3
GNPAT	ENST00000644483.1	c.26_27del	p.Ser9LeufsTer25	frameshift_variant, NMD_transcript_variant	1/17

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Rhizomelic chondrodysplasia punctata type 2 Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Baylor Genetics

Jul 03, 2023

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Computational scores

Source: dbNSFP v4.3

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-231377147;