Variant chr15-78149427-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005530.3(IDH3A):c.24T>C(p.Ser8=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 1,547,230 control chromosomes in the GnomAD database, including 198,719 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 23555 hom., cov: 33)

Exomes 𝑓: 0.50 ( 175164 hom. )

Consequence

IDH3A
NM_005530.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.108

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 15-78149427-T-C is Benign according to our data. Variant chr15-78149427-T-C is described in ClinVar as [Benign]. Clinvar id is 1169182.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.108 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.675 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.24T>C	p.Ser8=	synonymous_variant	1/11	ENST00000299518.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IDH3A	ENST00000299518.7 linkuse as main transcript	c.24T>C	p.Ser8=	synonymous_variant	1/11	1	NM_005530.3	P1	P50213-1

Frequencies

GnomAD3 genomes

AF:

0.547

AC:

83048

AN:

151924

Hom.:

23546

Cov.:

show subpopulations

Gnomad AFR

AF:

0.682

Gnomad AMI

AF:

0.565

Gnomad AMR

AF:

0.450

Gnomad ASJ

AF:

0.538

Gnomad EAS

AF:

0.324

Gnomad SAS

AF:

0.588

Gnomad FIN

AF:

0.526

Gnomad MID

AF:

0.631

Gnomad NFE

AF:

0.503

Gnomad OTH

AF:

0.519

GnomAD3 exomes

AF:

0.484

AC:

77655

AN:

160334

Hom.:

19291

AF XY:

0.497

AC XY:

44457

AN XY:

89534

show subpopulations

Gnomad AFR exome

AF:

0.661

Gnomad AMR exome

AF:

0.390

Gnomad ASJ exome

AF:

0.537

Gnomad EAS exome

AF:

0.308

Gnomad SAS exome

AF:

0.585

Gnomad FIN exome

AF:

0.506

Gnomad NFE exome

AF:

0.492

Gnomad OTH exome

AF:

0.483

GnomAD4 exome

AF:

0.498

AC:

695329

AN:

1395198

Hom.:

175164

Cov.:

AF XY:

0.501

AC XY:

346717

AN XY:

691764

show subpopulations

Gnomad4 AFR exome

AF:

0.688

Gnomad4 AMR exome

AF:

0.404

Gnomad4 ASJ exome

AF:

0.538

Gnomad4 EAS exome

AF:

0.315

Gnomad4 SAS exome

AF:

0.590

Gnomad4 FIN exome

AF:

0.518

Gnomad4 NFE exome

AF:

0.494

Gnomad4 OTH exome

AF:

0.503

GnomAD4 genome

AF:

0.547

AC:

83092

AN:

152032

Hom.:

23555

Cov.:

AF XY:

0.544

AC XY:

40443

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.682

Gnomad4 AMR

AF:

0.449

Gnomad4 ASJ

AF:

0.538

Gnomad4 EAS

AF:

0.324

Gnomad4 SAS

AF:

0.588

Gnomad4 FIN

AF:

0.526

Gnomad4 NFE

AF:

0.503

Gnomad4 OTH

AF:

0.517

Alfa

AF:

0.502

Hom.:

7078

Bravo

AF:

0.544

Asia WGS

AF:

0.479

AC:

1666

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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