NM_000182.5:c.67+51G>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000182.5(HADHA):c.67+51G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,542,746 control chromosomes in the GnomAD database, including 33,190 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2767 hom., cov: 33)

Exomes 𝑓: 0.20 ( 30423 hom. )

Consequence

HADHA
NM_000182.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.105

Variant links:

Genes affected

HADHA (HGNC:4801): (hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha) This gene encodes the alpha 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 alpha subunit catalyzing the 3-hydroxyacyl-CoA dehydrogenase and enoyl-CoA hydratase activities. Mutations in this gene result in trifunctional protein deficiency or LCHAD deficiency. 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. [provided by RefSeq, Jul 2008]

HADHA links:

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]

HADHB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 2-26244479-C-A is Benign according to our data. Variant chr2-26244479-C-A is described in ClinVar as [Benign]. Clinvar id is 676134.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HADHA	NM_000182.5 link	c.67+51G>T		intron_variant	Intron 1 of 19	ENST00000380649.8	NP_000173.2	P40939-1E9KL44

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HADHA	ENST00000380649.8 link	c.67+51G>T		intron_variant	Intron 1 of 19	1	NM_000182.5	ENSP00000370023.3		P40939-1

Frequencies

GnomAD3 genomes

AF:

0.178

AC:

27040

AN:

152106

Hom.:

2763

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0670

Gnomad AMI

AF:

0.277

Gnomad AMR

AF:

0.192

Gnomad ASJ

AF:

0.311

Gnomad EAS

AF:

0.153

Gnomad SAS

AF:

0.217

Gnomad FIN

AF:

0.294

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.214

Gnomad OTH

AF:

0.192

GnomAD3 exomes

AF:

0.215

AC:

33212

AN:

154134

Hom.:

3776

AF XY:

0.216

AC XY:

17754

AN XY:

82102

show subpopulations

Gnomad AFR exome

AF:

0.0605

Gnomad AMR exome

AF:

0.205

Gnomad ASJ exome

AF:

0.321

Gnomad EAS exome

AF:

0.154

Gnomad SAS exome

AF:

0.225

Gnomad FIN exome

AF:

0.287

Gnomad NFE exome

AF:

0.214

Gnomad OTH exome

AF:

0.227

GnomAD4 exome

AF:

0.204

AC:

284192

AN:

1390522

Hom.:

30423

Cov.:

AF XY:

0.205

AC XY:

140960

AN XY:

686644

show subpopulations

Gnomad4 AFR exome

AF:

0.0612

Gnomad4 AMR exome

AF:

0.204

Gnomad4 ASJ exome

AF:

0.322

Gnomad4 EAS exome

AF:

0.126

Gnomad4 SAS exome

AF:

0.224

Gnomad4 FIN exome

AF:

0.281

Gnomad4 NFE exome

AF:

0.203

Gnomad4 OTH exome

AF:

0.207

GnomAD4 genome

AF:

0.178

AC:

27061

AN:

152224

Hom.:

2767

Cov.:

AF XY:

0.183

AC XY:

13585

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0670

Gnomad4 AMR

AF:

0.192

Gnomad4 ASJ

AF:

0.311

Gnomad4 EAS

AF:

0.154

Gnomad4 SAS

AF:

0.217

Gnomad4 FIN

AF:

0.294

Gnomad4 NFE

AF:

0.214

Gnomad4 OTH

AF:

0.195

Alfa

AF:

0.211

Hom.:

643

Bravo

AF:

0.165

Asia WGS

AF:

0.236

AC:

821

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 18, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency

Benign:1

Jun 10, 2021

Genome-Nilou Lab

Significance: 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

-0.74

CADD

Benign

7.4

DANN

Benign

0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over