7-27543001-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_152740.4(HIBADH):āc.584A>Gā(p.Asn195Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000118 in 1,613,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000039 ( 0 hom., cov: 31)
Exomes š: 0.0000089 ( 0 hom. )
Consequence
HIBADH
NM_152740.4 missense
NM_152740.4 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 6.26
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.30546448).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HIBADH | NM_152740.4 | c.584A>G | p.Asn195Ser | missense_variant | 5/8 | ENST00000265395.7 | |
HIBADH | XM_047419834.1 | c.281A>G | p.Asn94Ser | missense_variant | 4/7 | ||
HIBADH | XM_047419835.1 | c.281A>G | p.Asn94Ser | missense_variant | 4/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HIBADH | ENST00000265395.7 | c.584A>G | p.Asn195Ser | missense_variant | 5/8 | 1 | NM_152740.4 | P1 | |
HIBADH | ENST00000425715.1 | c.413A>G | p.Asn138Ser | missense_variant | 4/6 | 2 | |||
HIBADH | ENST00000428288.2 | c.*303A>G | 3_prime_UTR_variant, NMD_transcript_variant | 4/7 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 152078Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000279 AC: 7AN: 250848Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135538
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GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461560Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727082
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GnomAD4 genome AF: 0.0000395 AC: 6AN: 152078Hom.: 0 Cov.: 31 AF XY: 0.0000673 AC XY: 5AN XY: 74284
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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 | Jun 27, 2022 | The c.584A>G (p.N195S) alteration is located in exon 5 (coding exon 5) of the HIBADH gene. This alteration results from a A to G substitution at nucleotide position 584, causing the asparagine (N) at amino acid position 195 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at