1-75762840-C-T

Variant names:

• chr1-75762840-C-T
• rs143911981
• NM_000016.6:c.*77C>T

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.*77C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00665 in 891,436 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0065 (16 hom., cov: 33)
  • Exomes 𝑓: 0.0067 (74 hom.)
• Consequence: ACADM NM_000016.6 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.251
• Publications: 1 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: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-75762840-C-T is Benign according to our data. Variant chr1-75762840-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 226053.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0627 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACADM	NM_000016.6	MANE Select	c.*77C>T		3_prime_UTR	Exon 12 of 12	NP_000007.1	A0A0S2Z366
	ACADM	NM_001286043.2		c.*77C>T		3_prime_UTR	Exon 13 of 13	NP_001272972.1	Q5T4U5
	ACADM	NM_001127328.3		c.*77C>T		3_prime_UTR	Exon 12 of 12	NP_001120800.1	P11310-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACADM	ENST00000370841.9	TSL:1 MANE Select	c.*77C>T		3_prime_UTR	Exon 12 of 12	ENSP00000359878.5	P11310-1
	ACADM	ENST00000370834.9	TSL:1	c.*77C>T		3_prime_UTR	Exon 13 of 13	ENSP00000359871.5	Q5T4U5
	ACADM	ENST00000541113.6	TSL:1	c.*77C>T		3_prime_UTR	Exon 11 of 11	ENSP00000442324.2	F6YB23

Frequencies

GnomAD3 genomes AF: 0.00655 AC: 996 AN: 152040 Hom.: 16 Cov.: 33

Gnomad AFR AF: 0.00147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0347

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00538

Gnomad FIN AF: 0.00595

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00418

Gnomad OTH AF: 0.00720

GnomAD4 exome AF: 0.00667 AC: 4933 AN: 739278 Hom.: 74 Cov.: 10 AF XY: 0.00636 AC XY: 2480 AN XY: 389698

African (AFR) AF: 0.00162 AC: 28 AN: 17310

American (AMR) AF: 0.0651 AC: 1887 AN: 28964

Ashkenazi Jewish (ASJ) AF: 0.00503 AC: 97 AN: 19300

East Asian (EAS) AF: 0.000265 AC: 9 AN: 33944

South Asian (SAS) AF: 0.00519 AC: 321 AN: 61804

European-Finnish (FIN) AF: 0.00631 AC: 302 AN: 47876

Middle Eastern (MID) AF: 0.000739 AC: 3 AN: 4058

European-Non Finnish (NFE) AF: 0.00424 AC: 2078 AN: 490556

Other (OTH) AF: 0.00586 AC: 208 AN: 35466

GnomAD4 genome AF: 0.00655 AC: 996 AN: 152158 Hom.: 16 Cov.: 33 AF XY: 0.00684 AC XY: 509 AN XY: 74378

African (AFR) AF: 0.00147 AC: 61 AN: 41556

American (AMR) AF: 0.0347 AC: 530 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.00539 AC: 26 AN: 4826

European-Finnish (FIN) AF: 0.00595 AC: 63 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00418 AC: 284 AN: 67944

Other (OTH) AF: 0.00712 AC: 15 AN: 2106

Alfa AF: 0.0100 Hom.: 9

Bravo AF: 0.00894

Asia WGS AF: 0.00667 AC: 23 AN: 3460

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Medium-chain acyl-coenzyme A dehydrogenase deficiency (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.85
DANN	Benign	0.48
PhyloP100		-0.25
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs143911981; hg19: chr1-76228525;