NM_000016.6:c.387+32C>G

Variant names:

• chr1-75733660-C-G
• rs2153126
• NM_000016.6:c.387+32C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000016.6(ACADM):​c.387+32C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 1,521,720 control chromosomes in the GnomAD database, including 75,110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (6987 hom., cov: 32)
  • Exomes 𝑓: 0.31 (68123 hom.)
• Consequence: ACADM NM_000016.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.39
• Publications: 9 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 1-75733660-C-G is Benign according to our data. Variant chr1-75733660-C-G is described in ClinVar as Benign. ClinVar VariationId is 254689.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACADM	NM_000016.6	c.387+32C>G		intron_variant	Intron 5 of 11	ENST00000370841.9	NP_000007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACADM	ENST00000370841.9	c.387+32C>G		intron_variant	Intron 5 of 11	1	NM_000016.6	ENSP00000359878.5

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45438 AN: 151734 Hom.: 6983 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.0353

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.295

GnomAD2 exomes AF: 0.276 AC: 69231 AN: 251068 AF XY: 0.273

Gnomad AFR exome AF: 0.289

Gnomad AMR exome AF: 0.308

Gnomad ASJ exome AF: 0.218

Gnomad EAS exome AF: 0.0261

Gnomad FIN exome AF: 0.282

Gnomad NFE exome AF: 0.327

Gnomad OTH exome AF: 0.301

GnomAD4 exome AF: 0.309 AC: 422845 AN: 1369868 Hom.: 68123 Cov.: 22 AF XY: 0.304 AC XY: 209067 AN XY: 686918

African (AFR) AF: 0.293 AC: 9240 AN: 31494

American (AMR) AF: 0.312 AC: 13911 AN: 44598

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 5508 AN: 25544

East Asian (EAS) AF: 0.0304 AC: 1191 AN: 39214

South Asian (SAS) AF: 0.197 AC: 16669 AN: 84430

European-Finnish (FIN) AF: 0.282 AC: 15017 AN: 53338

Middle Eastern (MID) AF: 0.256 AC: 1440 AN: 5636

European-Non Finnish (NFE) AF: 0.334 AC: 343029 AN: 1028284

Other (OTH) AF: 0.294 AC: 16840 AN: 57330

GnomAD4 genome AF: 0.299 AC: 45473 AN: 151852 Hom.: 6987 Cov.: 32 AF XY: 0.294 AC XY: 21837 AN XY: 74198

African (AFR) AF: 0.287 AC: 11886 AN: 41368

American (AMR) AF: 0.326 AC: 4983 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 744 AN: 3472

East Asian (EAS) AF: 0.0348 AC: 180 AN: 5168

South Asian (SAS) AF: 0.200 AC: 964 AN: 4808

European-Finnish (FIN) AF: 0.285 AC: 3000 AN: 10510

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22722 AN: 67940

Other (OTH) AF: 0.295 AC: 623 AN: 2112

Alfa AF: 0.297 Hom.: 1240

Bravo AF: 0.302

Asia WGS AF: 0.183 AC: 635 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Medium-chain acyl-coenzyme A dehydrogenase deficiency Benign:2

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Apr 06, 2018

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.072
DANN	Benign	0.63
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2153126; hg19: chr1-76199345;