NM_024586.6:c.458_459delGAinsAG

Variant names:

• chr1-51746753-GA-AG
• NM_024586.6:c.458_459delGAinsAG
• OSBPL9 p.Arg153Lys

Variant summary

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

The NM_024586.6(OSBPL9):​c.458_459delGAinsAG​(p.Arg153Lys) variant causes a missense change. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OSBPL9 NM_024586.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.52
• Publications: 0 publications found

Genes affected

OSBPL9 (HGNC:16386): (oxysterol binding protein like 9) This gene encodes a member of the oxysterol-binding protein (OSBP) family, a group of intracellular lipid receptors. Most members contain an N-terminal pleckstrin homology domain and a highly conserved C-terminal OSBP-like sterol-binding domain, although some members contain only the sterol-binding domain. This family member functions as a cholesterol transfer protein that regulates Golgi structure and function. Multiple transcript variants, most of which encode distinct isoforms, have been identified. Related pseudogenes have been identified on chromosomes 3, 11 and 12. [provided by RefSeq, Jul 2010]

OSBPL9 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• multiple congenital anomalies/dysmorphic syndrome

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024586.6. 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
	OSBPL9	NM_024586.6	MANE Select	c.458_459delGAinsAG	p.Arg153Lys	missense	N/A	NP_078862.4
	OSBPL9	NM_001416292.1		c.512_513delGAinsAG	p.Arg171Lys	missense	N/A	NP_001403221.1
	OSBPL9	NM_001416293.1		c.512_513delGAinsAG	p.Arg171Lys	missense	N/A	NP_001403222.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSBPL9	ENST00000428468.6	TSL:1 MANE Select	c.458_459delGAinsAG	p.Arg153Lys	missense	N/A	ENSP00000407168.1	Q96SU4-1
	OSBPL9	ENST00000453295.5	TSL:1	c.407_408delGAinsAG	p.Arg136Lys	missense	N/A	ENSP00000413263.1	Q96SU4-7
	OSBPL9	ENST00000361556.9	TSL:1	c.167_168delGAinsAG	p.Arg56Lys	missense	N/A	ENSP00000354970.5	Q96SU4-3

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.5

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: chr1-52212425;