dbSNP rs753411141: ACADM:c.-50A>C (chr1-75724738-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000016.6(ACADM):c.-50A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000719 in 1,390,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

ACADM
NM_000016.6 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.74

Publications

0 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: G2P, ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet

ACADM links:

ENSG00000293044 (HGNC:):

ENSG00000293044 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000016.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ACADM	NM_000016.6	MANE Select	c.-50A>C	5_prime_UTR	Exon 1 of 12	NP_000007.1	A0A0S2Z366
ACADM	NM_001286043.2		c.-50A>C	5_prime_UTR	Exon 1 of 13	NP_001272972.1	Q5T4U5
ACADM	NM_001127328.3		c.-50A>C	5_prime_UTR	Exon 1 of 12	NP_001120800.1	P11310-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ACADM	ENST00000370841.9	TSL:1 MANE Select	c.-50A>C	5_prime_UTR	Exon 1 of 12	ENSP00000359878.5	P11310-1
ACADM	ENST00000370834.9	TSL:1	c.-50A>C	5_prime_UTR	Exon 1 of 13	ENSP00000359871.5	Q5T4U5
ACADM	ENST00000541113.6	TSL:1	c.-50A>C	5_prime_UTR	Exon 1 of 11	ENSP00000442324.2	F6YB23

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.19e-7

AC:

AN:

1390676

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

690154

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28716

American (AMR)

AF:

0.00

AC:

AN:

35184

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23418

East Asian (EAS)

AF:

0.00

AC:

AN:

33290

South Asian (SAS)

AF:

0.00

AC:

AN:

78428

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51968

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5498

European-Non Finnish (NFE)

AF:

9.28e-7

AC:

AN:

1077064

Other (OTH)

AF:

0.00

AC:

AN:

57110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.033

(source)

DANN

Benign

0.68

PhyloP100

-1.7

PromoterAI

-0.089

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over