rs1061337

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000370841.9(ACADM):c.1161A>G(p.Val387=) 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
ENST00000370841.9 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.28

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 92254.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-75761337-A-G is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
ACADM	NM_000016.6 linkuse as main transcript	c.1161A>G	p.Val387=	synonymous_variant	11/12	ENST00000370841.9	NP_000007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACADM	ENST00000370841.9 linkuse as main transcript	c.1161A>G	p.Val387=	synonymous_variant	11/12	1	NM_000016.6	ENSP00000359878	P4	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

GnomAD3 exomes

AF:

0.234

AC:

58625

AN:

250748

Hom.:

7439

AF XY:

0.236

AC XY:

31940

AN XY:

135512

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 SAS exome

AF:

0.188

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

Gnomad4 AFR exome

AF:

0.150

Gnomad4 AMR exome

AF:

0.218

Gnomad4 ASJ exome

AF:

0.207

Gnomad4 EAS exome

AF:

0.0299

Gnomad4 SAS exome

AF:

0.184

Gnomad4 FIN exome

AF:

0.256

Gnomad4 NFE exome

AF:

0.300

Gnomad4 OTH exome

AF:

0.258

GnomAD4 genome

AF:

0.236

AC:

35835

AN:

152146

Hom.:

4582

Cov.:

AF XY:

0.232

AC XY:

17278

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.148

Gnomad4 AMR

AF:

0.254

Gnomad4 ASJ

AF:

0.206

Gnomad4 EAS

AF:

0.0336

Gnomad4 SAS

AF:

0.188

Gnomad4 FIN

AF:

0.257

Gnomad4 NFE

AF:

0.301

Gnomad4 OTH

AF:

0.241

Alfa

AF:

0.278

Hom.:

9114

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

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 17, 2021	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). -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 14, 2015	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Quest Diagnostics Nichols Institute San Juan Capistrano	Jul 19, 2017	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Medium-chain acyl-coenzyme A dehydrogenase deficiency

Benign:5

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 22, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	May 20, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 23810226) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

6.3

DANN

Benign

0.67

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over