NM_005530.3:c.27+1859G>A

Variant names:

• chr15-78151289-G-A
• rs11855354
• NM_005530.3:c.27+1859G>A

Variant summary

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

The NM_005530.3(IDH3A):​c.27+1859G>A 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 152,018 control chromosomes in the GnomAD database, including 23,186 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 (23175 hom., cov: 31)
  • Exomes 𝑓: 0.46 (11 hom.)
• Consequence: IDH3A NM_005530.3 intron
• Scores: Splicing: ADA: 0.00005058
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.521
• Publications: 8 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005530.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDH3A	NM_005530.3	MANE Select	c.27+1859G>A		intron	N/A	NP_005521.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDH3A	ENST00000299518.7	TSL:1 MANE Select	c.27+1859G>A		intron	N/A	ENSP00000299518.2
	IDH3A	ENST00000559889.5	TSL:1	n.53+1859G>A		intron	N/A
	IDH3A	ENST00000557826.5	TSL:4	c.-379G>A		splice_region	Exon 2 of 5	ENSP00000453480.1

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82258 AN: 151806 Hom.: 23165 Cov.: 31

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.517

GnomAD4 exome AF: 0.457 AC: 43 AN: 94 Hom.: 11 Cov.: 0 AF XY: 0.464 AC XY: 39 AN XY: 84

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.467 AC: 43 AN: 92

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.542 AC: 82308 AN: 151924 Hom.: 23175 Cov.: 31 AF XY: 0.537 AC XY: 39912 AN XY: 74268

African (AFR) AF: 0.681 AC: 28220 AN: 41438

American (AMR) AF: 0.448 AC: 6849 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 1867 AN: 3466

East Asian (EAS) AF: 0.298 AC: 1540 AN: 5164

South Asian (SAS) AF: 0.585 AC: 2819 AN: 4816

European-Finnish (FIN) AF: 0.487 AC: 5138 AN: 10554

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.502 AC: 34093 AN: 67908

Other (OTH) AF: 0.516 AC: 1085 AN: 2104

Alfa AF: 0.515 Hom.: 48607

Bravo AF: 0.543

Asia WGS AF: 0.464 AC: 1616 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.1
DANN	Benign	0.68
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000051
dbscSNV1_RF	Benign	0.0040
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: rs11855354; hg19: chr15-78443631;