Variant 15-78149544-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005530.3(IDH3A):c.27+114T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0577 in 891,654 control chromosomes in the GnomAD database, including 2,092 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.065 ( 379 hom., cov: 33)

Exomes 𝑓: 0.056 ( 1713 hom. )

Consequence

IDH3A
NM_005530.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.971

Variant links:

Genes affected

IDH3A (HGNC:5384): (isocitrate dehydrogenase (NAD(+)) 3 catalytic subunit alpha) 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 alpha subunit of one isozyme of NAD(+)-dependent isocitrate dehydrogenase. [provided by RefSeq, Jul 2008]

IDH3A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 15-78149544-T-G is Benign according to our data. Variant chr15-78149544-T-G is described in ClinVar as [Benign]. Clinvar id is 1227348.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IDH3A	NM_005530.3 linkuse as main transcript	c.27+114T>G		intron_variant		ENST00000299518.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IDH3A	ENST00000299518.7 linkuse as main transcript	c.27+114T>G		intron_variant		1	NM_005530.3	P1	P50213-1

Frequencies

GnomAD3 genomes

AF:

0.0647

AC:

9838

AN:

152052

Hom.:

381

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0912

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.0408

Gnomad ASJ

AF:

0.0885

Gnomad EAS

AF:

0.0285

Gnomad SAS

AF:

0.200

Gnomad FIN

AF:

0.0415

Gnomad MID

AF:

0.0828

Gnomad NFE

AF:

0.0499

Gnomad OTH

AF:

0.0574

GnomAD4 exome

AF:

0.0563

AC:

41632

AN:

739494

Hom.:

1713

AF XY:

0.0598

AC XY:

22667

AN XY:

378916

show subpopulations

Gnomad4 AFR exome

AF:

0.0891

Gnomad4 AMR exome

AF:

0.0254

Gnomad4 ASJ exome

AF:

0.0736

Gnomad4 EAS exome

AF:

0.0367

Gnomad4 SAS exome

AF:

0.167

Gnomad4 FIN exome

AF:

0.0407

Gnomad4 NFE exome

AF:

0.0478

Gnomad4 OTH exome

AF:

0.0584

GnomAD4 genome

AF:

0.0647

AC:

9838

AN:

152160

Hom.:

379

Cov.:

AF XY:

0.0659

AC XY:

4900

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0911

Gnomad4 AMR

AF:

0.0408

Gnomad4 ASJ

AF:

0.0885

Gnomad4 EAS

AF:

0.0288

Gnomad4 SAS

AF:

0.200

Gnomad4 FIN

AF:

0.0415

Gnomad4 NFE

AF:

0.0499

Gnomad4 OTH

AF:

0.0568

Alfa

AF:

0.0564

Hom.:

Bravo

AF:

0.0609

Asia WGS

AF:

0.127

AC:

438

AN:

3452

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

4.9

DANN

Benign

0.62

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over