rs59947000

Variant names:

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_7dupCTA(p.Thr2dup) variant causes a disruptive 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 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: 0.901

Variant links:

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]

HADHB links:

Genome browser will be placed here

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 rank	MANE	Protein	UniProt
HADHB	NM_000183.3 link	c.5_7dupCTA	p.Thr2dup	disruptive_inframe_insertion	Exon 2 of 16	ENST00000317799.10	NP_000174.1	P55084-1
HADHB	NM_001281512.2 link	c.5_7dupCTA	p.Thr2dup	disruptive_inframe_insertion	Exon 2 of 15		NP_001268441.1	P55084F5GZQ3
HADHB	XM_011532803.2 link	c.5_7dupCTA	p.Thr2dup	disruptive_inframe_insertion	Exon 2 of 16		XP_011531105.1	P55084-1
HADHB	NM_001281513.2 link	c.-145_-143dupCTA		5_prime_UTR_variant	Exon 2 of 17		NP_001268442.1	P55084-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HADHB	ENST00000317799.10 link	c.5_7dupCTA	p.Thr2dup	disruptive_inframe_insertion	Exon 2 of 16	1	NM_000183.3	ENSP00000325136.5		P55084-1

Frequencies

GnomAD3 genomes

AF:

0.868

AC:

131734

AN:

151840

Hom.:

58846

Cov.:

show subpopulations

Gnomad AFR

AF:

0.876

Gnomad AMI

AF:

0.913

Gnomad AMR

AF:

0.738

Gnomad ASJ

AF:

0.903

Gnomad EAS

AF:

0.183

Gnomad SAS

AF:

0.817

Gnomad FIN

AF:

0.938

Gnomad MID

AF:

0.972

Gnomad NFE

AF:

0.933

Gnomad OTH

AF:

0.861

GnomAD3 exomes

AF:

0.819

AC:

205645

AN:

250998

Hom.:

90048

AF XY:

0.834

AC XY:

113224

AN XY:

135752

show subpopulations

Gnomad AFR exome

AF:

0.877

Gnomad AMR exome

AF:

0.618

Gnomad ASJ exome

AF:

0.908

Gnomad EAS exome

AF:

0.178

Gnomad SAS exome

AF:

0.846

Gnomad FIN exome

AF:

0.938

Gnomad NFE exome

AF:

0.936

Gnomad OTH exome

AF:

0.870

GnomAD4 exome

AF:

0.877

AC:

1039351

AN:

1184466

Hom.:

470684

Cov.:

AF XY:

0.880

AC XY:

529990

AN XY:

602496

show subpopulations

Gnomad4 AFR exome

AF:

0.864

Gnomad4 AMR exome

AF:

0.634

Gnomad4 ASJ exome

AF:

0.901

Gnomad4 EAS exome

AF:

0.161

Gnomad4 SAS exome

AF:

0.843

Gnomad4 FIN exome

AF:

0.940

Gnomad4 NFE exome

AF:

0.923

Gnomad4 OTH exome

AF:

0.857

GnomAD4 genome

AF:

0.868

AC:

131841

AN:

151960

Hom.:

58895

Cov.:

AF XY:

0.860

AC XY:

63877

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.876

Gnomad4 AMR

AF:

0.738

Gnomad4 ASJ

AF:

0.903

Gnomad4 EAS

AF:

0.184

Gnomad4 SAS

AF:

0.817

Gnomad4 FIN

AF:

0.938

Gnomad4 NFE

AF:

0.933

Gnomad4 OTH

AF:

0.860

Alfa

AF:

0.897

Hom.:

40930

Bravo

AF:

0.847

Asia WGS

AF:

0.584

AC:

2031

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 -

Oct 02, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 27, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The variant is found in HADHB panel(s). -

Mitochondrial trifunctional protein deficiency

Benign:3

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Other:1

Department of Mental Retardation and Birth Defect Research, National Center of Neurology and Psychiatry

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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