2-111031628-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001142807.4(ACOXL):ā€‹c.1283T>Cā€‹(p.Val428Ala) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000041 ( 0 hom. )

Consequence

ACOXL
NM_001142807.4 missense, splice_region

Scores

4
15
Splicing: ADA: 0.9001
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.52
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.17523363).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ACOXLNM_001142807.4 linkuse as main transcriptc.1283T>C p.Val428Ala missense_variant, splice_region_variant 15/18 ENST00000439055.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ACOXLENST00000439055.6 linkuse as main transcriptc.1283T>C p.Val428Ala missense_variant, splice_region_variant 15/182 NM_001142807.4 Q9NUZ1-4
MIR4435-2HGENST00000645030.2 linkuse as main transcriptn.599+5148A>G intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152140
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251384
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135864
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461798
Hom.:
0
Cov.:
31
AF XY:
0.00000825
AC XY:
6
AN XY:
727212
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152140
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 29, 2023The c.1283T>C (p.V428A) alteration is located in exon 15 (coding exon 14) of the ACOXL gene. This alteration results from a T to C substitution at nucleotide position 1283, causing the valine (V) at amino acid position 428 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.34
BayesDel_addAF
Uncertain
0.088
D
BayesDel_noAF
Benign
-0.10
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0049
T;.;.;.
Eigen
Benign
0.11
Eigen_PC
Benign
0.18
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Benign
0.51
T;T;T;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.18
T;T;T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
1.6
L;.;.;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-1.4
N;N;N;D
REVEL
Benign
0.23
Sift
Benign
0.13
T;D;T;D
Sift4G
Benign
0.83
T;T;D;D
Polyphen
0.071
B;.;.;.
Vest4
0.51
MutPred
0.54
Loss of stability (P = 0.0063);.;.;.;
MVP
0.59
MPC
0.78
ClinPred
0.53
D
GERP RS
5.9
Varity_R
0.19
gMVP
0.10

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.90
dbscSNV1_RF
Benign
0.51
SpliceAI score (max)
0.40
Details are displayed if max score is > 0.2
DS_AL_spliceai
0.40
Position offset: -1

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs759297115; hg19: chr2-111789205; API