rs762083095

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_000017.4(ACADS):​c.842G>A​(p.Gly281Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging 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: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

ACADS
NM_000017.4 missense

Scores

17
1
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.60
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.992

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ACADSNM_000017.4 linkuse as main transcriptc.842G>A p.Gly281Asp missense_variant 7/10 ENST00000242592.9 NP_000008.1 P16219E5KSD5
ACADSNM_001302554.2 linkuse as main transcriptc.830G>A p.Gly277Asp missense_variant 7/10 NP_001289483.1 P16219E9PE82B4DUH1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ACADSENST00000242592.9 linkuse as main transcriptc.842G>A p.Gly281Asp missense_variant 7/101 NM_000017.4 ENSP00000242592.4 P16219
ACADSENST00000411593.2 linkuse as main transcriptc.830G>A p.Gly277Asp missense_variant 7/102 ENSP00000401045.2 E9PE82

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000400
AC:
1
AN:
249704
Hom.:
0
AF XY:
0.00000740
AC XY:
1
AN XY:
135158
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1460246
Hom.:
0
Cov.:
44
AF XY:
0.00
AC XY:
0
AN XY:
726540
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.47
D
BayesDel_noAF
Pathogenic
0.60
CADD
Pathogenic
33
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.98
D;D
Eigen
Pathogenic
1.1
Eigen_PC
Pathogenic
0.96
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
1.0
D;D
M_CAP
Pathogenic
0.37
D
MetaRNN
Pathogenic
0.99
D;D
MetaSVM
Pathogenic
0.98
D
MutationAssessor
Pathogenic
4.5
H;.
PrimateAI
Pathogenic
0.81
D
PROVEAN
Pathogenic
-6.9
D;D
REVEL
Pathogenic
0.99
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;D
Vest4
0.98
MutPred
0.96
Gain of relative solvent accessibility (P = 0.1259);.;
MVP
1.0
MPC
0.89
ClinPred
1.0
D
GERP RS
5.0
Varity_R
0.99
gMVP
0.99

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
Details are displayed if max score is > 0.2

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: rs762083095; hg19: chr12-121176382; API