rs112196218
Variant summary
Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_000182.5(HADHA):c.573+8dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00141 in 1,606,826 control chromosomes in the GnomAD database, including 18 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_000182.5 splice_region, intron
Scores
Clinical Significance
Conservation
Publications
- long chain 3-hydroxyacyl-CoA dehydrogenase deficiencyInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
- mitochondrial trifunctional protein deficiencyInheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
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ACMG classification
Our verdict: Benign. The variant received -16 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00555 AC: 845AN: 152154Hom.: 7 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.00229 AC: 575AN: 251216 AF XY: 0.00221 show subpopulations
GnomAD4 exome AF: 0.000973 AC: 1415AN: 1454554Hom.: 11 Cov.: 29 AF XY: 0.00110 AC XY: 795AN XY: 724208 show subpopulations
GnomAD4 genome AF: 0.00557 AC: 848AN: 152272Hom.: 7 Cov.: 32 AF XY: 0.00527 AC XY: 392AN XY: 74450 show subpopulations
ClinVar
Submissions by phenotype
not specified Benign:2
The variant is found in FAO-MET,UCD-MET panel(s). -
Variant summary: HADHA c.573+8dupT alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant changes to splicing, however, these predictions have not been assessed by functional studies. The variant allele was found at a frequency of 0.0026 in 276958 control chromosomes in the gnomAD database, including 8 homozygotes. The observed variant frequency is approximately 1.36 fold above the estimated maximal expected allele frequency for a pathogenic variant in HADHA causing Long Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency phenotype (0.0019), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.573+8dupT in individuals affected with Long Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign. -
Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency Benign:1
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not provided Benign:1
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Mitochondrial trifunctional protein deficiency;C3711645:Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at