rs13289

Positions:

• chr5-33986304-C-G
• chr5-33986304-C-T

Variant summary

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

The NM_014324.6(AMACR):​c.*2789G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 152,110 control chromosomes in the GnomAD database, including 21,944 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 0.52 (21943 hom., cov: 33)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: AMACR NM_014324.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710

Genes affected

AMACR (HGNC:451): (alpha-methylacyl-CoA racemase) This gene encodes a racemase. The encoded enzyme interconverts pristanoyl-CoA and C27-bile acylCoAs between their (R)- and (S)-stereoisomers. The conversion to the (S)-stereoisomers is necessary for degradation of these substrates by peroxisomal beta-oxidation. Encoded proteins from this locus localize to both mitochondria and peroxisomes. Mutations in this gene may be associated with adult-onset sensorimotor neuropathy, pigmentary retinopathy, and adrenomyeloneuropathy due to defects in bile acid synthesis. Alternatively spliced transcript variants have been described. Read-through transcription also exists between this gene and the upstream neighboring C1QTNF3 (C1q and tumor necrosis factor related protein 3) gene. [provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMACR	NM_014324.6	c.*2789G>C		3_prime_UTR_variant	5/5	ENST00000335606.11	NP_055139.4
AMACR	NM_203382.3	c.*3180G>C		3_prime_UTR_variant	4/4		NP_976316.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMACR	ENST00000335606.11	c.*2789G>C		3_prime_UTR_variant	5/5	1	NM_014324.6	ENSP00000334424	P1

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78813 AN: 151982 Hom.: 21939 Cov.: 33

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.619

Gnomad OTH AF: 0.510

GnomAD4 exome AF: 0.500 AC: 4 AN: 8 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 AFR exome AF: 0.250

Gnomad4 NFE exome AF: 0.750

GnomAD4 genome AF: 0.518 AC: 78832 AN: 152102 Hom.: 21943 Cov.: 33 AF XY: 0.516 AC XY: 38335 AN XY: 74352

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.521

Gnomad4 ASJ AF: 0.582

Gnomad4 EAS AF: 0.667

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.652

Gnomad4 NFE AF: 0.619

Gnomad4 OTH AF: 0.509

Alfa AF: 0.435 Hom.: 1312

Bravo AF: 0.509

Asia WGS AF: 0.435 AC: 1513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.92
DANN	Benign	0.55

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

Other links and lift over

dbSNP: rs13289; hg19: chr5-33986409;