Genetic Variant ACADL:p.Arg311Lys (chr2-210203383-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001608.4(ACADL):c.932G>A(p.Arg311Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,576 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R311M) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ACADL
NM_001608.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.60

Publications

0 publications found

Variant links:

Genes affected

ACADL (HGNC:88): (acyl-CoA dehydrogenase long chain) The protein encoded by this gene belongs to the acyl-CoA dehydrogenase family, which is a family of mitochondrial flavoenzymes involved in fatty acid and branched chain amino-acid metabolism. This protein is one of the four enzymes that catalyze the initial step of mitochondrial beta-oxidation of straight-chain fatty acid. Defects in this gene are the cause of long-chain acyl-CoA dehydrogenase (LCAD) deficiency, leading to nonketotic hypoglycemia. [provided by RefSeq, Jul 2008]

ACADL Gene-Disease associations (from GenCC):

long chain acyl-CoA dehydrogenase deficiency
Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACADL links:

ENSG00000279317 (HGNC:):

ENSG00000279317 links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001608.4. 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
	ACADL	NM_001608.4	MANE Select	c.932G>A	p.Arg311Lys	missense	Exon 8 of 11	NP_001599.1	P28330

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACADL	ENST00000233710.4	TSL:1 MANE Select	c.932G>A	p.Arg311Lys	missense	Exon 8 of 11	ENSP00000233710.3	P28330
ACADL	ENST00000862330.1		c.899G>A	p.Arg300Lys	missense	Exon 8 of 11	ENSP00000532389.1
ACADL	ENST00000862329.1		c.794G>A	p.Arg265Lys	missense	Exon 7 of 10	ENSP00000532388.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460576

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726600

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33448

American (AMR)

AF:

0.00

AC:

AN:

44664

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.00

AC:

AN:

39632

South Asian (SAS)

AF:

0.00

AC:

AN:

86220

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53310

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111100

Other (OTH)

AF:

0.00

AC:

AN:

60326

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

Exome Het

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.16

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.63

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.89

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.66

MetaSVM

Uncertain

0.65

MutationAssessor

Benign

1.2

PhyloP100

5.6

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.1

REVEL

Pathogenic

0.65

Sift

Benign

0.22

Sift4G

Benign

0.29

Polyphen

0.72

Vest4

0.53

MutPred

0.67

Gain of ubiquitination at R311 (P = 0.03)

MVP

0.96

MPC

0.41

ClinPred

0.95

GERP RS

5.4

Varity_R

0.49

gMVP

0.86

Mutation Taster

=61/39

polymorphism

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over