20-2658516-T-C
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001330763.2(IDH3B):āc.1157A>Gā(p.Asn386Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0104 in 1,613,486 control chromosomes in the GnomAD database, including 1,373 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.054 ( 726 hom., cov: 32)
Exomes š: 0.0059 ( 647 hom. )
Consequence
IDH3B
NM_001330763.2 missense
NM_001330763.2 missense
Scores
3
1
7
Clinical Significance
Conservation
PhyloP100: 6.83
Genes affected
IDH3B (HGNC:5385): (isocitrate dehydrogenase (NAD(+)) 3 non-catalytic subunit beta) Isocitrate dehydrogenases catalyze the oxidative decarboxylation of isocitrate to 2-oxoglutarate. These enzymes belong to two distinct subclasses, one of which utilizes NAD(+) as the electron acceptor and the other NADP(+). Five isocitrate dehydrogenases have been reported: three NAD(+)-dependent isocitrate dehydrogenases, which localize to the mitochondrial matrix, and two NADP(+)-dependent isocitrate dehydrogenases, one of which is mitochondrial and the other predominantly cytosolic. NAD(+)-dependent isocitrate dehydrogenases catalyze the allosterically regulated rate-limiting step of the tricarboxylic acid cycle. Each isozyme is a heterotetramer that is composed of two alpha subunits, one beta subunit, and one gamma subunit. The protein encoded by this gene is the beta subunit of one isozyme of NAD(+)-dependent isocitrate dehydrogenase. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Sep 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0015983284).
BP6
Variant 20-2658516-T-C is Benign according to our data. Variant chr20-2658516-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 338008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IDH3B | NM_006899.5 | c.*235A>G | 3_prime_UTR_variant | 12/12 | ENST00000380843.9 | NP_008830.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IDH3B | ENST00000474315.5 | c.1157A>G | p.Asn386Ser | missense_variant | 13/13 | 1 | ENSP00000482773.1 | |||
IDH3B | ENST00000380843.9 | c.*235A>G | 3_prime_UTR_variant | 12/12 | 1 | NM_006899.5 | ENSP00000370223.4 |
Frequencies
GnomAD3 genomes AF: 0.0540 AC: 8194AN: 151630Hom.: 725 Cov.: 32
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GnomAD3 exomes AF: 0.0146 AC: 3665AN: 250816Hom.: 284 AF XY: 0.0104 AC XY: 1406AN XY: 135586
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GnomAD4 exome AF: 0.00591 AC: 8639AN: 1461738Hom.: 647 Cov.: 34 AF XY: 0.00517 AC XY: 3757AN XY: 727154
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GnomAD4 genome AF: 0.0540 AC: 8200AN: 151748Hom.: 726 Cov.: 32 AF XY: 0.0520 AC XY: 3856AN XY: 74170
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 12, 2021 | - - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Retinitis pigmentosa Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
MetaRNN
Benign
T
Sift4G
Benign
T
Vest4
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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