7-27543070-G-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_152740.4(HIBADH):c.515C>T(p.Thr172Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000583 in 1,613,524 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000063 ( 0 hom. )
Consequence
HIBADH
NM_152740.4 missense
NM_152740.4 missense
Scores
12
5
2
Clinical Significance
Conservation
PhyloP100: 9.99
Genes affected
HIBADH (HGNC:4907): (3-hydroxyisobutyrate dehydrogenase) This gene encodes a mitochondrial 3-hydroxyisobutyrate dehydrogenase enzyme. The encoded protein plays a critical role in the catabolism of L-valine by catalyzing the oxidation of 3-hydroxyisobutyrate to methylmalonate semialdehyde. [provided by RefSeq, Nov 2011]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.907
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HIBADH | NM_152740.4 | c.515C>T | p.Thr172Met | missense_variant | 5/8 | ENST00000265395.7 | |
HIBADH | XM_047419834.1 | c.212C>T | p.Thr71Met | missense_variant | 4/7 | ||
HIBADH | XM_047419835.1 | c.212C>T | p.Thr71Met | missense_variant | 4/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HIBADH | ENST00000265395.7 | c.515C>T | p.Thr172Met | missense_variant | 5/8 | 1 | NM_152740.4 | P1 | |
HIBADH | ENST00000425715.1 | c.344C>T | p.Thr115Met | missense_variant | 4/6 | 2 | |||
HIBADH | ENST00000428288.2 | c.*234C>T | 3_prime_UTR_variant, NMD_transcript_variant | 4/7 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152084Hom.: 0 Cov.: 31
GnomAD3 genomes
AF:
AC:
2
AN:
152084
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 250732Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135486
GnomAD3 exomes
AF:
AC:
5
AN:
250732
Hom.:
AF XY:
AC XY:
3
AN XY:
135486
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000630 AC: 92AN: 1461440Hom.: 0 Cov.: 31 AF XY: 0.0000660 AC XY: 48AN XY: 726998
GnomAD4 exome
AF:
AC:
92
AN:
1461440
Hom.:
Cov.:
31
AF XY:
AC XY:
48
AN XY:
726998
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000132 AC: 2AN: 152084Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74308
GnomAD4 genome
AF:
AC:
2
AN:
152084
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
74308
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
AF:
AC:
5
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 17, 2023 | The c.515C>T (p.T172M) alteration is located in exon 5 (coding exon 5) of the HIBADH gene. This alteration results from a C to T substitution at nucleotide position 515, causing the threonine (T) at amino acid position 172 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at