7-27531323-C-A
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_152740.4(HIBADH):c.721G>T(p.Ala241Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00123 in 1,613,020 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).
Frequency
Genomes: 𝑓 0.00083 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0013 ( 3 hom. )
Consequence
HIBADH
NM_152740.4 missense
NM_152740.4 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 4.08
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 Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.032527238).
BP6
Variant 7-27531323-C-A is Benign according to our data. Variant chr7-27531323-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3035525.Status of the report is no_assertion_criteria_provided, 0 stars.
BS2
High Homozygotes in GnomAdExome4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HIBADH | NM_152740.4 | c.721G>T | p.Ala241Ser | missense_variant | 7/8 | ENST00000265395.7 | |
HIBADH | XM_047419834.1 | c.418G>T | p.Ala140Ser | missense_variant | 6/7 | ||
HIBADH | XM_047419835.1 | c.418G>T | p.Ala140Ser | missense_variant | 6/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HIBADH | ENST00000265395.7 | c.721G>T | p.Ala241Ser | missense_variant | 7/8 | 1 | NM_152740.4 | P1 | |
HIBADH | ENST00000425715.1 | c.550G>T | p.Ala184Ser | missense_variant | 6/6 | 2 | |||
HIBADH | ENST00000428288.2 | c.*440G>T | 3_prime_UTR_variant, NMD_transcript_variant | 6/7 | 3 |
Frequencies
GnomAD3 genomes AF: 0.000835 AC: 127AN: 152154Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000866 AC: 217AN: 250616Hom.: 0 AF XY: 0.000820 AC XY: 111AN XY: 135442
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GnomAD4 exome AF: 0.00127 AC: 1851AN: 1460748Hom.: 3 Cov.: 31 AF XY: 0.00123 AC XY: 893AN XY: 726578
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GnomAD4 genome AF: 0.000834 AC: 127AN: 152272Hom.: 0 Cov.: 32 AF XY: 0.000725 AC XY: 54AN XY: 74452
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
HIBADH-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 22, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
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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