rs3839049
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PM4_SupportingBP6_Very_StrongBA1
The NM_000183.3(HADHB):c.5_7dup(p.Thr2dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.87 ( 58895 hom., cov: 0)
Exomes 𝑓: 0.88 ( 470684 hom. )
Consequence
HADHB
NM_000183.3 inframe_insertion
NM_000183.3 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.901
Genes affected
HADHB (HGNC:4803): (hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta) This gene encodes the beta subunit of the mitochondrial trifunctional protein, which catalyzes the last three steps of mitochondrial beta-oxidation of long chain fatty acids. The mitochondrial membrane-bound heterocomplex is composed of four alpha and four beta subunits, with the beta subunit catalyzing the 3-ketoacyl-CoA thiolase activity. The encoded protein can also bind RNA and decreases the stability of some mRNAs. The genes of the alpha and beta subunits of the mitochondrial trifunctional protein are located adjacent to each other in the human genome in a head-to-head orientation. Mutations in this gene result in trifunctional protein deficiency. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
PM4
?
Nonframeshift variant in NON repetitive region in NM_000183.3. Strenght limited to Supporting due to length of the change: 1aa.
BP6
?
Variant 2-26254257-G-GACT is Benign according to our data. Variant chr2-26254257-G-GACT is described in ClinVar as [Benign]. Clinvar id is 92600.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HADHB | NM_000183.3 | c.5_7dup | p.Thr2dup | inframe_insertion | 2/16 | ENST00000317799.10 | |
HADHB | NM_001281512.2 | c.5_7dup | p.Thr2dup | inframe_insertion | 2/15 | ||
HADHB | XM_011532803.2 | c.5_7dup | p.Thr2dup | inframe_insertion | 2/16 | ||
HADHB | NM_001281513.2 | c.-145_-143dup | 5_prime_UTR_variant | 2/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HADHB | ENST00000317799.10 | c.5_7dup | p.Thr2dup | inframe_insertion | 2/16 | 1 | NM_000183.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.868 AC: 131734AN: 151840Hom.: 58846 Cov.: 0
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GnomAD3 exomes AF: 0.819 AC: 205645AN: 250998Hom.: 90048 AF XY: 0.834 AC XY: 113224AN XY: 135752
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GnomAD4 exome AF: 0.877 AC: 1039351AN: 1184466Hom.: 470684 Cov.: 19 AF XY: 0.880 AC XY: 529990AN XY: 602496
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GnomAD4 genome ? AF: 0.868 AC: 131841AN: 151960Hom.: 58895 Cov.: 0 AF XY: 0.860 AC XY: 63877AN XY: 74258
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ClinVar
Significance: Benign
Submissions summary: Benign:6Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 27, 2013 | The variant is found in HADHB panel(s). - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 28, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 83% of total chromosomes in ExAC - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 02, 2013 | - - |
Mitochondrial trifunctional protein deficiency Benign:3
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
not provided Other:1
not provided, no classification provided | literature only | Department of Mental Retardation and Birth Defect Research, National Center of Neurology and Psychiatry | - | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at