X-153790717-C-T

Variant names:

• chrX-153790717-C-T
• rs17429
• NM_004135.4:c.123+93G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.466
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• retinitis pigmentosa

  Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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	c.123+93G>A		intron_variant	Intron 2 of 12	ENST00000217901.10	NP_004126.1
IDH3G	NM_174869.3	c.123+93G>A		intron_variant	Intron 2 of 11		NP_777358.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0656 AC: 7409 AN: 113010 Hom.: 596 Cov.: 25

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.: 18 AF XY: 0.00629 AC XY: 1749 AN XY: 278159

African (AFR) AF: 0.234 AC: 5605 AN: 23980

American (AMR) AF: 0.0130 AC: 449 AN: 34648

Ashkenazi Jewish (ASJ) AF: 0.000109 AC: 2 AN: 18348

East Asian (EAS) AF: 0.00 AC: 0 AN: 29581

South Asian (SAS) AF: 0.000650 AC: 33 AN: 50737

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40198

Middle Eastern (MID) AF: 0.00911 AC: 35 AN: 3842

European-Non Finnish (NFE) AF: 0.000437 AC: 319 AN: 729647

Other (OTH) AF: 0.0158 AC: 664 AN: 41952

GnomAD4 genome AF: 0.0656 AC: 7415 AN: 113061 Hom.: 596 Cov.: 25 AF XY: 0.0594 AC XY: 2092 AN XY: 35223

African (AFR) AF: 0.225 AC: 6969 AN: 31016

American (AMR) AF: 0.0288 AC: 313 AN: 10851

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2661

East Asian (EAS) AF: 0.00 AC: 0 AN: 3613

South Asian (SAS) AF: 0.000709 AC: 2 AN: 2820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6288

Middle Eastern (MID) AF: 0.00917 AC: 2 AN: 218

European-Non Finnish (NFE) AF: 0.000768 AC: 41 AN: 53358

Other (OTH) AF: 0.0569 AC: 88 AN: 1547

Alfa AF: 0.0205 Hom.: 174

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
PhyloP100		-0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17429; hg19: chrX-153056172;