15-78171144-G-A

Variant names:

• chr15-78171144-G-A
• rs3825847
• NM_015162.5:c.*300C>T

Variant summary

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

The NM_015162.5(ACSBG1):​c.*300C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0654 in 257,354 control chromosomes in the GnomAD database, including 752 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 0.064 (358 hom., cov: 33)
  • Exomes 𝑓: 0.068 (394 hom.)
• Consequence: ACSBG1 NM_015162.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.520
• Publications: 10 publications found

Genes affected

ACSBG1 (HGNC:29567): (acyl-CoA synthetase bubblegum family member 1) The protein encoded by this gene possesses long-chain acyl-CoA synthetase activity. It is thought to play a central role in brain very long-chain fatty acids metabolism and myelinogenesis. [provided by RefSeq, Jul 2008]

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=-0.62).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015162.5. 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
	ACSBG1	NM_015162.5	MANE Select	c.*300C>T		3_prime_UTR	Exon 14 of 14	NP_055977.3
	IDH3A	NM_005530.3	MANE Select	c.*2139G>A		3_prime_UTR	Exon 11 of 11	NP_005521.1
	ACSBG1	NM_001199377.2		c.*300C>T		3_prime_UTR	Exon 14 of 14	NP_001186306.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSBG1	ENST00000258873.9	TSL:1 MANE Select	c.*300C>T		3_prime_UTR	Exon 14 of 14	ENSP00000258873.4
	IDH3A	ENST00000299518.7	TSL:1 MANE Select	c.*2139G>A		3_prime_UTR	Exon 11 of 11	ENSP00000299518.2
	IDH3A	ENST00000557960.1	TSL:3	n.*167G>A		non_coding_transcript_exon	Exon 3 of 3	ENSP00000453459.1

Frequencies

GnomAD3 genomes AF: 0.0636 AC: 9673 AN: 152164 Hom.: 359 Cov.: 33

Gnomad AFR AF: 0.0912

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0409

Gnomad ASJ AF: 0.0884

Gnomad EAS AF: 0.0288

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.0316

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.0496

Gnomad OTH AF: 0.0580

GnomAD4 exome AF: 0.0680 AC: 7147 AN: 105070 Hom.: 394 Cov.: 0 AF XY: 0.0772 AC XY: 4274 AN XY: 55350

African (AFR) AF: 0.0896 AC: 308 AN: 3436

American (AMR) AF: 0.0406 AC: 193 AN: 4758

Ashkenazi Jewish (ASJ) AF: 0.0956 AC: 266 AN: 2782

East Asian (EAS) AF: 0.0299 AC: 168 AN: 5618

South Asian (SAS) AF: 0.183 AC: 2472 AN: 13490

European-Finnish (FIN) AF: 0.0468 AC: 234 AN: 4998

Middle Eastern (MID) AF: 0.0514 AC: 22 AN: 428

European-Non Finnish (NFE) AF: 0.0497 AC: 3174 AN: 63816

Other (OTH) AF: 0.0540 AC: 310 AN: 5744

GnomAD4 genome AF: 0.0635 AC: 9675 AN: 152284 Hom.: 358 Cov.: 33 AF XY: 0.0641 AC XY: 4773 AN XY: 74466

African (AFR) AF: 0.0911 AC: 3784 AN: 41556

American (AMR) AF: 0.0409 AC: 625 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0884 AC: 307 AN: 3472

East Asian (EAS) AF: 0.0291 AC: 151 AN: 5190

South Asian (SAS) AF: 0.190 AC: 915 AN: 4828

European-Finnish (FIN) AF: 0.0316 AC: 335 AN: 10596

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0496 AC: 3377 AN: 68030

Other (OTH) AF: 0.0574 AC: 121 AN: 2108

Alfa AF: 0.0562 Hom.: 514

Bravo AF: 0.0608

Asia WGS AF: 0.124 AC: 431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	11
DANN	Benign	0.89
PhyloP100		0.52
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: rs3825847; hg19: chr15-78463486;