1-231265356-GT-TC

Variant names:

• chr1-231265356-GT-TC
• NM_014236.4:c.632_633delGTinsTC
• GNPAT p.Arg211Leu

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM5 PP3

The NM_014236.4(GNPAT):​c.632_633delGTinsTC​(p.Arg211Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. R211C) has been classified as Likely pathogenic.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GNPAT NM_014236.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.47
• Publications: 0 publications found

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]

GNPAT Gene-Disease associations (from GenCC):

• glyceronephosphate O-acyltransferase deficiency

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• rhizomelic chondrodysplasia punctata type 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM5: Other missense variant is known to change same aminoacid residue: Variant chr1-231265355-C-T is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 6842.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014236.4. 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
	GNPAT	NM_014236.4	MANE Select	c.632_633delGTinsTC	p.Arg211Leu	missense	N/A	NP_055051.1	O15228-1
	GNPAT	NM_001316350.2		c.449_450delGTinsTC	p.Arg150Leu	missense	N/A	NP_001303279.1	O15228-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNPAT	ENST00000366647.9	TSL:1 MANE Select	c.632_633delGTinsTC	p.Arg211Leu	missense	N/A	ENSP00000355607.4	O15228-1
	GNPAT	ENST00000851685.1		c.665_666delGTinsTC	p.Arg222Leu	missense	N/A	ENSP00000521744.1
	GNPAT	ENST00000926541.1		c.632_633delGTinsTC	p.Arg211Leu	missense	N/A	ENSP00000596600.1

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.5

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-231401102;