rs777002501

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP2PP5

The NM_000017.4(ACADS):c.505A>C(p.Thr169Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,613,798 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T169T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000053 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000022 ( 1 hom. )

Consequence

ACADS
NM_000017.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:2U:5

Conservation

PhyloP100: 0.682

Publications

3 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, Orphanet, Labcorp Genetics (formerly Invitae), G2P, ClinGen

ACADS links:

ENSG00000255946 (HGNC:):

ENSG00000255946 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_000017.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 27 curated pathogenic missense variants (we use a threshold of 10). The gene has 8 curated benign missense variants. Gene score misZ: 0.58444 (below the threshold of 3.09). Trascript score misZ: 0.78549 (below the threshold of 3.09). GenCC associations: The gene is linked to short chain acyl-CoA dehydrogenase deficiency.

PP5

Variant 12-120737869-A-C is Pathogenic according to our data. Variant chr12-120737869-A-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 551228.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000017.4. 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
	ACADS	NM_000017.4	MANE Select	c.505A>C	p.Thr169Pro	missense	Exon 5 of 10	NP_000008.1	P16219
	ACADS	NM_001302554.2		c.473-180A>C		intron	N/A	NP_001289483.1	E9PE82

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACADS	ENST00000242592.9	TSL:1 MANE Select	c.505A>C	p.Thr169Pro	missense	Exon 5 of 10	ENSP00000242592.4	P16219
ACADS	ENST00000946559.1		c.505A>C	p.Thr169Pro	missense	Exon 5 of 10	ENSP00000616618.1
ACADS	ENST00000893619.1		c.505A>C	p.Thr169Pro	missense	Exon 5 of 10	ENSP00000563678.1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

151950

Hom.:

Cov.:

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:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000438

AC:

AN:

250984

AF XY:

0.0000516

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:

0.0000219

AC:

AN:

1461730

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

727162

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000371

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53382

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111908

Other (OTH)

AF:

0.00

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152068

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41478

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00166

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67966

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000325

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Deficiency of butyryl-CoA dehydrogenase (7)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.65

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Pathogenic

0.42

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.94

Eigen

Benign

-0.0050

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.54

LIST_S2

Uncertain

0.93

M_CAP

Uncertain

0.26

MetaRNN

Uncertain

0.70

MetaSVM

Pathogenic

0.87

MutationAssessor

Pathogenic

3.4

PhyloP100

0.68

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-4.2

REVEL

Pathogenic

0.77

Sift

Benign

0.034

Sift4G

Uncertain

0.016

Varity_R

0.96

gMVP

0.93

Mutation Taster

=17/83

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over