rs12903696

Variant names:

• chr15-78146676-T-C
• rs12903696
• XR_007064725.1:n.1169A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_007064725.1(LOC124903534):​n.1169A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 152,056 control chromosomes in the GnomAD database, including 24,002 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 0.55 (24001 hom., cov: 32)
  • Exomes 𝑓: 0.40 (1 hom.)
• Consequence: LOC124903534 XR_007064725.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.758

Genes affected

LOC124903534 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124903534	XR_007064725.1	n.1169A>G		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IDH3A	ENST00000558605.1	n.409+86T>C		intron_variant	Intron 2 of 3	4

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83481 AN: 151896 Hom.: 23983 Cov.: 32

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.521

GnomAD4 exome AF: 0.405 AC: 17 AN: 42 Hom.: 1 AF XY: 0.433 AC XY: 13 AN XY: 30

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.406

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.550 AC: 83543 AN: 152014 Hom.: 24001 Cov.: 32 AF XY: 0.546 AC XY: 40556 AN XY: 74320

Gnomad4 AFR AF: 0.707

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.537

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.586

Gnomad4 FIN AF: 0.497

Gnomad4 NFE AF: 0.502

Gnomad4 OTH AF: 0.519

Alfa AF: 0.520 Hom.: 3610

Bravo AF: 0.551

Asia WGS AF: 0.469 AC: 1631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.40
DANN	Benign	0.65

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12903696; hg19: chr15-78439018;