17-75953459-G-A

Variant names:

• chr17-75953459-G-A
• NM_004035.7:c.936C>T
• ACOX1 p.Ile312Ile

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_004035.7(ACOX1):​c.936C>T​(p.Ile312Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACOX1 NM_004035.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 0 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: Ambry Genetics, G2P, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)
• Mitchell syndrome

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

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP7: Synonymous conserved (PhyloP=1.13 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004035.7. 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
	ACOX1	NM_004035.7	MANE Select	c.936C>T	p.Ile312Ile	synonymous	Exon 7 of 14	NP_004026.2
	ACOX1	NM_007292.6		c.936C>T	p.Ile312Ile	synonymous	Exon 7 of 14	NP_009223.2
	ACOX1	NM_001185039.2		c.822C>T	p.Ile274Ile	synonymous	Exon 7 of 14	NP_001171968.1	Q15067-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACOX1	ENST00000293217.10	TSL:1 MANE Select	c.936C>T	p.Ile312Ile	synonymous	Exon 7 of 14	ENSP00000293217.4	Q15067-2
	ACOX1	ENST00000301608.9	TSL:1	c.936C>T	p.Ile312Ile	synonymous	Exon 7 of 14	ENSP00000301608.4	Q15067-1
	ACOX1	ENST00000949477.1		c.1134C>T	p.Ile378Ile	synonymous	Exon 9 of 16	ENSP00000619536.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461520 Hom.: 0 Cov.: 55 AF XY: 0.00 AC XY: 0 AN XY: 727076

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111798

Other (OTH) AF: 0.00 AC: 0 AN: 60366

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	13
DANN	Benign	0.80
PhyloP100		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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: chr17-73949540;