X-153790717-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004135.4(IDH3G):​c.123+93G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000885 in 113,025 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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 0.0000088 (0 hom., 1 hem., cov: 25)
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004135.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDH3G	NM_004135.4	MANE Select	c.123+93G>T		intron	N/A	NP_004126.1
	IDH3G	NM_174869.3		c.123+93G>T		intron	N/A	NP_777358.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDH3G	ENST00000217901.10	TSL:1 MANE Select	c.123+93G>T		intron	N/A	ENSP00000217901.5
	IDH3G	ENST00000370092.7	TSL:5	c.123+93G>T		intron	N/A	ENSP00000359110.3
	IDH3G	ENST00000370093.5	TSL:2	c.123+93G>T		intron	N/A	ENSP00000359111.1

Frequencies

GnomAD3 genomes AF: 0.00000885 AC: 1 AN: 113025 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.0000323

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 18

GnomAD4 genome AF: 0.00000885 AC: 1 AN: 113025 Hom.: 0 Cov.: 25 AF XY: 0.0000284 AC XY: 1 AN XY: 35171

African (AFR) AF: 0.0000323 AC: 1 AN: 30963

American (AMR) AF: 0.00 AC: 0 AN: 10839

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 3624

South Asian (SAS) AF: 0.00 AC: 0 AN: 2828

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53366

Other (OTH) AF: 0.00 AC: 0 AN: 1528

Alfa AF: 0.00 Hom.: 174

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.077
DANN	Benign	0.72
PhyloP100		-0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;