GeneBe

NM_014362.4:c.1127_1128delTT

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PVS1_ModeratePM2

The NM_014362.4(HIBCH):​c.1127_1128delTT​(p.Phe376fs) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000206 in 1,455,652 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

HIBCH
NM_014362.4 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.99

Publications

1 publications found
Variant links:
Genes affected
HIBCH (HGNC:4908): (3-hydroxyisobutyryl-CoA hydrolase) This gene encodes the enzyme responsible for hydrolysis of both HIBYL-CoA and beta-hydroxypropionyl-CoA. Mutations in this gene have been associated with 3-hyroxyisobutyryl-CoA hydrolase deficiency. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]
HIBCH Gene-Disease associations (from GenCC):
  • 3-hydroxyisobutyryl-CoA hydrolase deficiency
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, ClinGen
  • Leigh syndrome
    Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0293 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HIBCHNM_014362.4 linkc.1127_1128delTT p.Phe376fs frameshift_variant Exon 14 of 14 ENST00000359678.10 NP_055177.2 Q6NVY1-1A0A140VJL0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HIBCHENST00000359678.10 linkc.1127_1128delTT p.Phe376fs frameshift_variant Exon 14 of 14 1 NM_014362.4 ENSP00000352706.5 Q6NVY1-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1455652
Hom.:
0
AF XY:
0.00000276
AC XY:
2
AN XY:
724546
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33346
American (AMR)
AF:
0.00
AC:
0
AN:
44700
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26078
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39642
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86064
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53354
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4632
European-Non Finnish (NFE)
AF:
0.00000271
AC:
3
AN:
1107766
Other (OTH)
AF:
0.00
AC:
0
AN:
60070
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.458
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
7.0

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

Other links and lift over

dbSNP: rs863225062; hg19: chr2-191069875; API