rs1061337

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000016.6(ACADM):c.1161A>G(p.Val387Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,613,518 control chromosomes in the GnomAD database, including 62,204 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. V387V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.24 ( 4582 hom., cov: 32)

Exomes 𝑓: 0.27 ( 57622 hom. )

Consequence

ACADM
NM_000016.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 1.28

Publications

29 publications found

Variant links:

Genes affected

ACADM (HGNC:89): (acyl-CoA dehydrogenase medium chain) This gene encodes the medium-chain specific (C4 to C12 straight chain) acyl-Coenzyme A dehydrogenase. The homotetramer enzyme catalyzes the initial step of the mitochondrial fatty acid beta-oxidation pathway. Defects in this gene cause medium-chain acyl-CoA dehydrogenase deficiency, a disease characterized by hepatic dysfunction, fasting hypoglycemia, and encephalopathy, which can result in infantile death. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACADM Gene-Disease associations (from GenCC):

medium chain acyl-CoA dehydrogenase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, ClinGen, Orphanet

ACADM links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 1-75761337-A-G is Benign according to our data. Variant chr1-75761337-A-G is described in ClinVar as Benign. ClinVar VariationId is 92254.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.28 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACADM	NM_000016.6 link	c.1161A>G	p.Val387Val	synonymous_variant	Exon 11 of 12	ENST00000370841.9	NP_000007.1	P11310-1A0A0S2Z366

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACADM	ENST00000370841.9 link	c.1161A>G	p.Val387Val	synonymous_variant	Exon 11 of 12	1	NM_000016.6	ENSP00000359878.5		P11310-1

Frequencies

GnomAD3 genomes

AF:

0.236

AC:

35826

AN:

152028

Hom.:

4582

Cov.:

show subpopulations

Gnomad AFR

AF:

0.148

Gnomad AMI

AF:

0.308

Gnomad AMR

AF:

0.254

Gnomad ASJ

AF:

0.206

Gnomad EAS

AF:

0.0341

Gnomad SAS

AF:

0.188

Gnomad FIN

AF:

0.257

Gnomad MID

AF:

0.258

Gnomad NFE

AF:

0.301

Gnomad OTH

AF:

0.242

GnomAD2 exomes

AF:

0.234

AC:

58625

AN:

250748

AF XY:

0.236

show subpopulations

Gnomad AFR exome

AF:

0.146

Gnomad AMR exome

AF:

0.214

Gnomad ASJ exome

AF:

0.209

Gnomad EAS exome

AF:

0.0254

Gnomad FIN exome

AF:

0.257

Gnomad NFE exome

AF:

0.295

Gnomad OTH exome

AF:

0.265

GnomAD4 exome

AF:

0.274

AC:

400907

AN:

1461372

Hom.:

57622

Cov.:

AF XY:

0.272

AC XY:

197437

AN XY:

727024

show subpopulations

African (AFR)

AF:

0.150

AC:

5020

AN:

33472

American (AMR)

AF:

0.218

AC:

9768

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.207

AC:

5399

AN:

26126

East Asian (EAS)

AF:

0.0299

AC:

1187

AN:

39688

South Asian (SAS)

AF:

0.184

AC:

15863

AN:

86248

European-Finnish (FIN)

AF:

0.256

AC:

13682

AN:

53360

Middle Eastern (MID)

AF:

0.244

AC:

1406

AN:

5766

European-Non Finnish (NFE)

AF:

0.300

AC:

333020

AN:

1111614

Other (OTH)

AF:

0.258

AC:

15562

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

15197

30394

45592

60789

75986

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10792

21584

32376

43168

53960

<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:

0.236

AC:

35835

AN:

152146

Hom.:

4582

Cov.:

AF XY:

0.232

AC XY:

17278

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.148

AC:

6144

AN:

41530

American (AMR)

AF:

0.254

AC:

3880

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.206

AC:

714

AN:

3470

East Asian (EAS)

AF:

0.0336

AC:

174

AN:

5174

South Asian (SAS)

AF:

0.188

AC:

907

AN:

4822

European-Finnish (FIN)

AF:

0.257

AC:

2716

AN:

10576

Middle Eastern (MID)

AF:

0.267

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.301

AC:

20430

AN:

67972

Other (OTH)

AF:

0.241

AC:

511

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1392

2784

4176

5568

6960

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

378

756

1134

1512

1890

<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:

0.273

Hom.:

20191

Bravo

AF:

0.230

Asia WGS

AF:

0.163

AC:

568

AN:

3478

EpiCase

AF:

0.297

EpiControl

AF:

0.297

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Sep 14, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 19, 2017

Quest Diagnostics Nichols Institute San Juan Capistrano

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 17, 2021

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The p.Val391Val variant in ACADM is not expected to have clinical significance because it has been identified in 29% (37908/128544) of European chromosomes, including 5448 homozygotes, by gnomAD (http://gnomad.broadinstitute.org). -

Medium-chain acyl-coenzyme A dehydrogenase deficiency

Benign:5

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

May 20, 2019

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Nov 05, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 23810226) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

6.3

(source)

DANN

Benign

0.67

PhyloP100

1.3

Mutation Taster

=98/2

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over