Genetic Variant IDH3G:c.123+93G>A (chrX-153790717-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004135.4(IDH3G):c.123+93G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 1,085,994 control chromosomes in the GnomAD database, including 1,120 homozygotes. There are 3,841 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.066 ( 596 hom., 2092 hem., cov: 25)

Exomes 𝑓: 0.0073 ( 524 hom. 1749 hem. )

Consequence

IDH3G
NM_004135.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.466

Variant links:

Genes affected

IDH3G (HGNC:5386): (isocitrate dehydrogenase (NAD(+)) 3 non-catalytic subunit gamma) 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 gamma subunit of one isozyme of NAD(+)-dependent isocitrate dehydrogenase. This gene is a candidate gene for periventricular heterotopia. Several alternatively spliced transcript variants of this gene have been described, but only some of their full length natures have been determined. [provided by RefSeq, Jul 2008]

IDH3G links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IDH3G	NM_004135.4 link	c.123+93G>A		intron_variant	Intron 2 of 12	ENST00000217901.10	NP_004126.1	P51553-1
IDH3G	NM_174869.3 link	c.123+93G>A		intron_variant	Intron 2 of 11		NP_777358.1	P51553-2O15384

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IDH3G	ENST00000217901.10 link	c.123+93G>A		intron_variant	Intron 2 of 12	1	NM_004135.4	ENSP00000217901.5		P51553-1

Frequencies

GnomAD3 genomes

AF:

0.0656

AC:

7409

AN:

113010

Hom.:

596

Cov.:

AF XY:

0.0594

AC XY:

2087

AN XY:

35162

show subpopulations

Gnomad AFR

AF:

0.225

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0289

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00141

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0126

Gnomad NFE

AF:

0.000768

Gnomad OTH

AF:

0.0576

GnomAD4 exome

AF:

0.00730

AC:

7107

AN:

972933

Hom.:

524

Cov.:

AF XY:

0.00629

AC XY:

1749

AN XY:

278159

show subpopulations

Gnomad4 AFR exome

AF:

0.234

Gnomad4 AMR exome

AF:

0.0130

Gnomad4 ASJ exome

AF:

0.000109

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000650

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000437

Gnomad4 OTH exome

AF:

0.0158

GnomAD4 genome

AF:

0.0656

AC:

7415

AN:

113061

Hom.:

596

Cov.:

AF XY:

0.0594

AC XY:

2092

AN XY:

35223

show subpopulations

Gnomad4 AFR

AF:

0.225

Gnomad4 AMR

AF:

0.0288

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000709

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000768

Gnomad4 OTH

AF:

0.0569

Alfa

AF:

0.0109

Hom.:

Bravo

AF:

0.0763

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.065

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over