3-197511986-C-T
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP3BP4_ModerateBP6BS2
The NM_203314.3(BDH1):c.941G>A(p.Arg314His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 1,611,480 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).
Frequency
Genomes: 𝑓 0.0011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0015 ( 5 hom. )
Consequence
BDH1
NM_203314.3 missense
NM_203314.3 missense
Scores
11
4
3
Clinical Significance
Conservation
PhyloP100: 7.91
Genes affected
BDH1 (HGNC:1027): (3-hydroxybutyrate dehydrogenase 1) This gene encodes a member of the short-chain dehydrogenase/reductase gene family. The encoded protein forms a homotetrameric lipid-requiring enzyme of the mitochondrial membrane and has a specific requirement for phosphatidylcholine for optimal enzymatic activity. The encoded protein catalyzes the interconversion of acetoacetate and (R)-3-hydroxybutyrate, the two major ketone bodies produced during fatty acid catabolism. Alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
PP3
Multiple lines of computational evidence support a deleterious effect 9: AlphaMissense, BayesDel_noAF, Cadd, Dann, Eigen, MutationAssessor, phyloP100way_vertebrate, PROVEAN, REVEL [when BayesDel_addAF, max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]
BP4
Computational evidence support a benign effect (MetaRNN=0.21549278).
BP6
Variant 3-197511986-C-T is Benign according to our data. Variant chr3-197511986-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3052892.Status of the report is no_assertion_criteria_provided, 0 stars.
BS2
High Homozygotes in GnomAdExome4 at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BDH1 | NM_203314.3 | c.941G>A | p.Arg314His | missense_variant | 8/8 | ENST00000392379.6 | NP_976059.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BDH1 | ENST00000392379.6 | c.941G>A | p.Arg314His | missense_variant | 8/8 | 5 | NM_203314.3 | ENSP00000376184.1 |
Frequencies
GnomAD3 genomes AF: 0.00112 AC: 171AN: 152106Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000958 AC: 238AN: 248542Hom.: 1 AF XY: 0.000947 AC XY: 127AN XY: 134072
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GnomAD4 exome AF: 0.00148 AC: 2164AN: 1459374Hom.: 5 Cov.: 31 AF XY: 0.00145 AC XY: 1049AN XY: 725756
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GnomAD4 genome AF: 0.00112 AC: 171AN: 152106Hom.: 0 Cov.: 33 AF XY: 0.00104 AC XY: 77AN XY: 74312
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
BDH1-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 14, 2022 | 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
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D;D;D;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
M;M;M;.
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D;D
Sift4G
Pathogenic
D;D;D;D
Polyphen
D;D;D;.
Vest4
MVP
MPC
ClinPred
T
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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