NM_000017.4:c.360+21C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000017.4(ACADS):​c.360+21C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,413,228 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ACADS
NM_000017.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0240

Publications

0 publications found
Variant links:
Genes affected
ACADS (HGNC:90): (acyl-CoA dehydrogenase short chain) This gene encodes a tetrameric mitochondrial flavoprotein, which is a member of the acyl-CoA dehydrogenase family. This enzyme catalyzes the initial step of the mitochondrial fatty acid beta-oxidation pathway. Mutations in this gene have been associated with short-chain acyl-CoA dehydrogenase (SCAD) deficiency. Alternative splicing results in two variants which encode different isoforms. [provided by RefSeq, Oct 2014]
ACADS Gene-Disease associations (from GenCC):
  • short chain acyl-CoA dehydrogenase deficiency
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Orphanet, ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ACADSNM_000017.4 linkc.360+21C>T intron_variant Intron 3 of 9 ENST00000242592.9 NP_000008.1 P16219E5KSD5
ACADSNM_001302554.2 linkc.360+21C>T intron_variant Intron 3 of 9 NP_001289483.1 P16219E9PE82B4DUH1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ACADSENST00000242592.9 linkc.360+21C>T intron_variant Intron 3 of 9 1 NM_000017.4 ENSP00000242592.4 P16219
ACADSENST00000539690.1 linkn.493C>T non_coding_transcript_exon_variant Exon 3 of 3 2
ACADSENST00000411593.2 linkc.360+21C>T intron_variant Intron 3 of 9 2 ENSP00000401045.2 E9PE82
ENSG00000255946ENST00000724268.1 linkn.305-6868G>A intron_variant Intron 1 of 1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD2 exomes
AF:
0.00000580
AC:
1
AN:
172436
AF XY:
0.0000109
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 FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000142
AC:
2
AN:
1413228
Hom.:
0
Cov.:
34
AF XY:
0.00000143
AC XY:
1
AN XY:
698694
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
32286
American (AMR)
AF:
0.00
AC:
0
AN:
37926
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25368
East Asian (EAS)
AF:
0.00
AC:
0
AN:
36948
South Asian (SAS)
AF:
0.0000124
AC:
1
AN:
80782
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
49474
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5702
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1086280
Other (OTH)
AF:
0.0000171
AC:
1
AN:
58462
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.600
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
0.98
DANN
Benign
0.91
PhyloP100
0.024

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

Publications

Other links and lift over

dbSNP: rs372974263; hg19: chr12-121174959; API