2-111031700-C-G

Variant names:

• chr2-111031700-C-G
• NM_001142807.4:c.1355C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001142807.4(ACOXL):​c.1355C>G​(p.Ala452Gly) variant causes a missense 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACOXL NM_001142807.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.64
• Publications: 0 publications found

Genes affected

ACOXL (HGNC:25621): (acyl-CoA oxidase like) Predicted to enable acyl-CoA oxidase activity; fatty acid binding activity; and flavin adenine dinucleotide binding activity. Predicted to be involved in fatty acid beta-oxidation using acyl-CoA oxidase and lipid homeostasis. Predicted to be located in peroxisomal matrix. Predicted to be active in peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

MIR4435-2HG (HGNC:35163): (MIR4435-2 host gene)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40237373).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142807.4. 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
	ACOXL	NM_001142807.4	MANE Select	c.1355C>G	p.Ala452Gly	missense	Exon 15 of 18	NP_001136279.1	Q9NUZ1-4
	ACOXL	NM_001437600.1		c.1445C>G	p.Ala482Gly	missense	Exon 16 of 19	NP_001424529.1	A0A7I2V3X2
	ACOXL	NM_001371254.1		c.1445C>G	p.Ala482Gly	missense	Exon 16 of 19	NP_001358183.1	Q9NUZ1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACOXL	ENST00000439055.6	TSL:2 MANE Select	c.1355C>G	p.Ala452Gly	missense	Exon 15 of 18	ENSP00000407761.1	Q9NUZ1-4
	ACOXL	ENST00000417074.5	TSL:1	c.869C>G	p.Ala290Gly	missense	Exon 9 of 12	ENSP00000387832.1	A0A0C4DG10
	ACOXL	ENST00000957119.1		c.1487C>G	p.Ala496Gly	missense	Exon 17 of 20	ENSP00000627178.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.18
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.6
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.26
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.015	D
Polyphen		1.0	D
Vest4		0.56
MutPred		0.68		Loss of stability (P = 0.0071)
MVP		0.65
MPC		0.64
ClinPred		0.95	D
GERP RS		3.1
Varity_R		0.64
gMVP		0.14
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

hg19: chr2-111789277;