15-78159661-C-T

Variant names:

• chr15-78159661-C-T
• rs8032618
• NM_005530.3:c.175-431C>T

Variant summary

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

The NM_005530.3(IDH3A):​c.175-431C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 151,928 control chromosomes in the GnomAD database, including 23,172 homozygotes. 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 0.54 (23172 hom., cov: 31)
• Consequence: IDH3A NM_005530.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.785
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• retinitis pigmentosa

  Inheritance: AR Classification: STRONG Submitted by: G2P
• retinitis pigmentosa 90

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• 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 rank	MANE	Protein	UniProt
IDH3A	NM_005530.3	c.175-431C>T		intron_variant	Intron 3 of 10	ENST00000299518.7	NP_005521.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IDH3A	ENST00000299518.7	c.175-431C>T		intron_variant	Intron 3 of 10	1	NM_005530.3	ENSP00000299518.2

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82260 AN: 151810 Hom.: 23162 Cov.: 31

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.518

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.542 AC: 82310 AN: 151928 Hom.: 23172 Cov.: 31 AF XY: 0.537 AC XY: 39910 AN XY: 74256

African (AFR) AF: 0.682 AC: 28244 AN: 41422

American (AMR) AF: 0.448 AC: 6849 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 1866 AN: 3468

East Asian (EAS) AF: 0.298 AC: 1536 AN: 5160

South Asian (SAS) AF: 0.577 AC: 2773 AN: 4810

European-Finnish (FIN) AF: 0.489 AC: 5150 AN: 10540

Middle Eastern (MID) AF: 0.627 AC: 183 AN: 292

European-Non Finnish (NFE) AF: 0.502 AC: 34111 AN: 67946

Other (OTH) AF: 0.516 AC: 1087 AN: 2106

Alfa AF: 0.509 Hom.: 11331

Bravo AF: 0.543

Asia WGS AF: 0.461 AC: 1605 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.5
DANN	Benign	0.90
PhyloP100		-0.79
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: rs8032618; hg19: chr15-78452003;