chr11-134253620-G-T

Variant names:

• chr11-134253620-G-T
• rs35181923
• NM_014384.3:c.20G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001441138.1(ACAD8):​c.-105G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,427,200 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: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: ACAD8 NM_001441138.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.314
• 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]

THYN1 (HGNC:29560): (thymocyte nuclear protein 1) This gene encodes a protein that is highly conserved among vertebrates and plant species and may be involved in the induction of apoptosis. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

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 (MetaRNN=0.06035608).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001441138.1. 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
	ACAD8	NM_014384.3	MANE Select	c.20G>T	p.Arg7Leu	missense	Exon 1 of 11	NP_055199.1	Q9UKU7-1
	ACAD8	NM_001441138.1		c.-105G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	NP_001428067.1
	ACAD8	NM_001441136.1		c.20G>T	p.Arg7Leu	missense	Exon 1 of 11	NP_001428065.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACAD8	ENST00000281182.9	TSL:1 MANE Select	c.20G>T	p.Arg7Leu	missense	Exon 1 of 11	ENSP00000281182.5	Q9UKU7-1
	ACAD8	ENST00000527082.5	TSL:1	n.44G>T		non_coding_transcript_exon	Exon 1 of 4
	ACAD8	ENST00000869565.1		c.20G>T	p.Arg7Leu	missense	Exon 1 of 12	ENSP00000539624.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1427200 Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1 AN XY: 707810

African (AFR) AF: 0.00 AC: 0 AN: 32674

American (AMR) AF: 0.00 AC: 0 AN: 39932

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25518

East Asian (EAS) AF: 0.00 AC: 0 AN: 37442

South Asian (SAS) AF: 0.00 AC: 0 AN: 82520

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45658

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5710

European-Non Finnish (NFE) AF: 9.10e-7 AC: 1 AN: 1098562

Other (OTH) AF: 0.00 AC: 0 AN: 59184

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.082	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	1.1
DANN	Benign	0.92
DEOGEN2	Benign	0.30	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.58	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.060	T
MetaSVM	Uncertain	0.13	D
MutationAssessor	Benign	0.34	N
PhyloP100		-0.31
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.18
Sift	Benign	0.67	T
Sift4G	Benign	0.65	T
Polyphen		0.0	B
Vest4		0.10
MutPred		0.54		Loss of methylation at R7 (P = 0.0151)
MVP		0.71
MPC		0.18
ClinPred		0.072	T
GERP RS		-1.6
PromoterAI		0.033	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.048
gMVP		0.67
Mutation Taster		=95/5	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: rs35181923; hg19: chr11-134123514;