11-134253627-C-T

Variant names:

• chr11-134253627-C-T
• rs2136068044
• NM_014384.3:c.27C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_014384.3(ACAD8):​c.27C>T​(p.Phe9Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACAD8 NM_014384.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.645
• Publications: 0 publications found

Genes affected

ACAD8 (HGNC:87): (acyl-CoA dehydrogenase family member 8) This gene encodes a member of the acyl-CoA dehydrogenase family of enzymes that catalyze the dehydrogenation of acyl-CoA derivatives in the metabolism of fatty acids or branch chained amino acids. The encoded protein is a mitochondrial enzyme that functions in catabolism of the branched-chain amino acid valine. Defects in this gene are the cause of isobutyryl-CoA dehydrogenase deficiency.[provided by RefSeq, Nov 2009]

ACAD8 Gene-Disease associations (from GenCC):

• isobutyryl-CoA dehydrogenase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 11-134253627-C-T is Benign according to our data. Variant chr11-134253627-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1139584.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.645 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACAD8	NM_014384.3	c.27C>T	p.Phe9Phe	synonymous_variant	Exon 1 of 11	ENST00000281182.9	NP_055199.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACAD8	ENST00000281182.9	c.27C>T	p.Phe9Phe	synonymous_variant	Exon 1 of 11	1	NM_014384.3	ENSP00000281182.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1430234 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 709478

African (AFR) AF: 0.00 AC: 0 AN: 32802

American (AMR) AF: 0.00 AC: 0 AN: 40444

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25578

East Asian (EAS) AF: 0.00 AC: 0 AN: 37648

South Asian (SAS) AF: 0.00 AC: 0 AN: 82774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46290

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099692

Other (OTH) AF: 0.00 AC: 0 AN: 59276

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Deficiency of isobutyryl-CoA dehydrogenase Benign:1

Oct 06, 2020

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely 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	-0.61
CADD	Benign	6.7
DANN	Benign	0.85
PhyloP100		-0.65
PromoterAI		0.023	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2136068044; hg19: chr11-134123521;