NM_000182.5:c.*302G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000182.5(HADHA):c.*302G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 511,080 control chromosomes in the GnomAD database, including 10,723 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2659 hom., cov: 33)

Exomes 𝑓: 0.20 ( 8064 hom. )

Consequence

HADHA
NM_000182.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0970

Publications

9 publications found

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:

GAREM2 (HGNC:27172): (GRB2 associated regulator of MAPK1 subtype 2)

GAREM2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

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

BP6

Variant 2-26190948-C-T is Benign according to our data. Variant chr2-26190948-C-T is described in ClinVar as [Benign]. Clinvar id is 335371.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HADHA	NM_000182.5 link	c.*302G>A		3_prime_UTR_variant	Exon 20 of 20	ENST00000380649.8	NP_000173.2	P40939-1E9KL44
GAREM2	XM_011532567.4 link	c.1683+3633C>T		intron_variant	Intron 6 of 6		XP_011530869.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HADHA	ENST00000380649.8 link	c.*302G>A		3_prime_UTR_variant	Exon 20 of 20	1	NM_000182.5	ENSP00000370023.3		P40939-1

Frequencies

GnomAD3 genomes

AF:

0.174

AC:

26512

AN:

152118

Hom.:

2655

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0657

Gnomad AMI

AF:

0.276

Gnomad AMR

AF:

0.184

Gnomad ASJ

AF:

0.308

Gnomad EAS

AF:

0.142

Gnomad SAS

AF:

0.212

Gnomad FIN

AF:

0.293

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.210

Gnomad OTH

AF:

0.187

GnomAD4 exome

AF:

0.203

AC:

73006

AN:

358844

Hom.:

8064

Cov.:

AF XY:

0.205

AC XY:

38875

AN XY:

189988

show subpopulations

African (AFR)

AF:

0.0624

AC:

666

AN:

10668

American (AMR)

AF:

0.190

AC:

2992

AN:

15788

Ashkenazi Jewish (ASJ)

AF:

0.314

AC:

3436

AN:

10942

East Asian (EAS)

AF:

0.114

AC:

2584

AN:

22700

South Asian (SAS)

AF:

0.220

AC:

9506

AN:

43142

European-Finnish (FIN)

AF:

0.272

AC:

5567

AN:

20464

Middle Eastern (MID)

AF:

0.228

AC:

353

AN:

1548

European-Non Finnish (NFE)

AF:

0.206

AC:

43765

AN:

212916

Other (OTH)

AF:

0.200

AC:

4137

AN:

20676

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

2775

5551

8326

11102

13877

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.174

AC:

26534

AN:

152236

Hom.:

2659

Cov.:

AF XY:

0.179

AC XY:

13317

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0657

AC:

2731

AN:

41558

American (AMR)

AF:

0.184

AC:

2822

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.308

AC:

1069

AN:

3470

East Asian (EAS)

AF:

0.143

AC:

743

AN:

5178

South Asian (SAS)

AF:

0.213

AC:

1026

AN:

4824

European-Finnish (FIN)

AF:

0.293

AC:

3107

AN:

10594

Middle Eastern (MID)

AF:

0.255

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.210

AC:

14308

AN:

67990

Other (OTH)

AF:

0.190

AC:

401

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1083

2166

3249

4332

5415

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.196

Hom.:

1061

Bravo

AF:

0.160

Asia WGS

AF:

0.229

AC:

798

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 19, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Mitochondrial trifunctional protein deficiency

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

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

6.0

(source)

DANN

Benign

0.80

PhyloP100

-0.097

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

NM_000182.5:c.*302G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over