Genetic Variant IDH3G:p.His301His (chrX-153786822-A-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP7BS2

The NM_004135.4(IDH3G):c.903T>C(p.His301His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000364 in 1,208,502 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 21 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., 2 hem., cov: 25)

Exomes 𝑓: 0.000037 ( 0 hom. 19 hem. )

Consequence

IDH3G
NM_004135.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.29

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

retinitis pigmentosa
Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

IDH3G links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP7

Synonymous conserved (PhyloP=-2.29 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDH3G	NM_004135.4	MANE Select	c.903T>C	p.His301His	synonymous	Exon 10 of 13	NP_004126.1	P51553-1
	IDH3G	NM_174869.3		c.903T>C	p.His301His	synonymous	Exon 10 of 12	NP_777358.1	P51553-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IDH3G	ENST00000217901.10	TSL:1 MANE Select	c.903T>C	p.His301His	synonymous	Exon 10 of 13	ENSP00000217901.5	P51553-1
IDH3G	ENST00000454076.5	TSL:1	c.318T>C	p.His106His	synonymous	Exon 3 of 6	ENSP00000400115.1	H0Y5Q7
IDH3G	ENST00000958656.1		c.1002T>C	p.His334His	synonymous	Exon 11 of 14	ENSP00000628715.1

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

113606

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000562

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000385

AC:

AN:

181681

AF XY:

0.0000600

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000626

Gnomad NFE exome

AF:

0.0000742

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000374

AC:

AN:

1094896

Hom.:

Cov.:

AF XY:

0.0000526

AC XY:

AN XY:

361082

show subpopulations

African (AFR)

AF:

0.0000379

AC:

AN:

26366

American (AMR)

AF:

0.00

AC:

AN:

35072

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19346

East Asian (EAS)

AF:

0.00

AC:

AN:

30138

South Asian (SAS)

AF:

0.00

AC:

AN:

54051

European-Finnish (FIN)

AF:

0.0000252

AC:

AN:

39695

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4123

European-Non Finnish (NFE)

AF:

0.0000429

AC:

AN:

840128

Other (OTH)

AF:

0.0000653

AC:

AN:

45977

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000264

AC:

AN:

113606

Hom.:

Cov.:

AF XY:

0.0000560

AC XY:

AN XY:

35738

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31364

American (AMR)

AF:

0.00

AC:

AN:

10894

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2664

East Asian (EAS)

AF:

0.00

AC:

AN:

3603

South Asian (SAS)

AF:

0.00

AC:

AN:

2822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6381

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.0000562

AC:

AN:

53404

Other (OTH)

AF:

0.00

AC:

AN:

1545

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.26

(source)

DANN

Benign

0.59

PhyloP100

-2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over