chr17-75960255-CAAGTTCCAGGCGGGCATG-C

Variant names:

• chr17-75960255-CAAGTTCCAGGCGGGCATG-C
• rs387906248
• NM_004035.7:c.372_389delCATGCCCGCCTGGAACTT

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM4 PP3 PP5

The NM_004035.7(ACOX1):​c.372_389delCATGCCCGCCTGGAACTT​(p.Phe124_Asn129del) variant causes a disruptive inframe deletion 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 DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. F124F) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACOX1 NM_004035.7 disruptive_inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.85
• Publications: 2 publications found

Genes affected

ACOX1 (HGNC:119): (acyl-CoA oxidase 1) The protein encoded by this gene is the first enzyme of the fatty acid beta-oxidation pathway, which catalyzes the desaturation of acyl-CoAs to 2-trans-enoyl-CoAs. It donates electrons directly to molecular oxygen, thereby producing hydrogen peroxide. Defects in this gene result in pseudoneonatal adrenoleukodystrophy, a disease that is characterized by accumulation of very long chain fatty acids. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACOX1 Gene-Disease associations (from GenCC):

• peroxisomal acyl-CoA oxidase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Ambry Genetics, Orphanet
• Mitchell syndrome

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_004035.7.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant 17-75960255-CAAGTTCCAGGCGGGCATG-C is Pathogenic according to our data. Variant chr17-75960255-CAAGTTCCAGGCGGGCATG-C is described in CliVar as Pathogenic. Clinvar id is 1503.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-75960255-CAAGTTCCAGGCGGGCATG-C is described in CliVar as Pathogenic. Clinvar id is 1503.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-75960255-CAAGTTCCAGGCGGGCATG-C is described in CliVar as Pathogenic. Clinvar id is 1503.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-75960255-CAAGTTCCAGGCGGGCATG-C is described in CliVar as Pathogenic. Clinvar id is 1503.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-75960255-CAAGTTCCAGGCGGGCATG-C is described in CliVar as Pathogenic. Clinvar id is 1503.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-75960255-CAAGTTCCAGGCGGGCATG-C is described in CliVar as Pathogenic. Clinvar id is 1503.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-75960255-CAAGTTCCAGGCGGGCATG-C is described in CliVar as Pathogenic. Clinvar id is 1503.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-75960255-CAAGTTCCAGGCGGGCATG-C is described in CliVar as Pathogenic. Clinvar id is 1503.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-75960255-CAAGTTCCAGGCGGGCATG-C is described in CliVar as Pathogenic. Clinvar id is 1503.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-75960255-CAAGTTCCAGGCGGGCATG-C is described in CliVar as Pathogenic. Clinvar id is 1503.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-75960255-CAAGTTCCAGGCGGGCATG-C is described in CliVar as Pathogenic. Clinvar id is 1503.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-75960255-CAAGTTCCAGGCGGGCATG-C is described in CliVar as Pathogenic. Clinvar id is 1503.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-75960255-CAAGTTCCAGGCGGGCATG-C is described in CliVar as Pathogenic. Clinvar id is 1503.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-75960255-CAAGTTCCAGGCGGGCATG-C is described in CliVar as Pathogenic. Clinvar id is 1503.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-75960255-CAAGTTCCAGGCGGGCATG-C is described in CliVar as Pathogenic. Clinvar id is 1503.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACOX1	NM_004035.7	c.372_389delCATGCCCGCCTGGAACTT	p.Phe124_Asn129del	disruptive_inframe_deletion	Exon 3 of 14	ENST00000293217.10	NP_004026.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACOX1	ENST00000293217.10	c.372_389delCATGCCCGCCTGGAACTT	p.Phe124_Asn129del	disruptive_inframe_deletion	Exon 3 of 14	1	NM_004035.7	ENSP00000293217.4

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: no assertion criteria provided

Submissions by phenotype

Acyl-CoA oxidase deficiency Pathogenic:1

Sep 01, 2007

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.8
Mutation Taster		=10/190	disease causing (ClinVar)

Splicing

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

Other links and lift over

dbSNP: rs387906248; hg19: chr17-73956336;