5-33987289-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_014324.6(AMACR):c.*1804G>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 0.00955 in 152,494 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0095 (11 hom., cov: 33)
  • Exomes 𝑓: 0.014 (0 hom.)
• Consequence: AMACR NM_014324.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0140

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]

C1QTNF3-AMACR (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 5-33987289-C-A is Benign according to our data. Variant chr5-33987289-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 353228.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00955 (1454/152272) while in subpopulation SAS AF= 0.0317 (153/4824). AF 95% confidence interval is 0.0276. There are 11 homozygotes in gnomad4. There are 740 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMACR	NM_014324.6	c.*1804G>T		3_prime_UTR_variant	5/5	ENST00000335606.11
C1QTNF3-AMACR	NR_037951.1	n.3309G>T		non_coding_transcript_exon_variant	9/9
AMACR	NM_001167595.2	c.*1019G>T		3_prime_UTR_variant	6/6
AMACR	NM_203382.3	c.*2195G>T		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMACR	ENST00000335606.11	c.*1804G>T		3_prime_UTR_variant	5/5	1	NM_014324.6	P1
AMACR	ENST00000382072.6	c.*2195G>T		3_prime_UTR_variant	4/4	1

Frequencies

GnomAD3 genomes AF: 0.00959 AC: 1459 AN: 152154 Hom.: 12 Cov.: 33

Gnomad AFR AF: 0.00630

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0185

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0321

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.00919

Gnomad OTH AF: 0.0163

GnomAD4 exome AF: 0.0135 AC: 3 AN: 222 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 116

Gnomad4 AMR exome AF: 0.00

Gnomad4 SAS exome AF: 0.0146

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00955 AC: 1454 AN: 152272 Hom.: 11 Cov.: 33 AF XY: 0.00994 AC XY: 740 AN XY: 74454

Gnomad4 AFR AF: 0.00628

Gnomad4 AMR AF: 0.0185

Gnomad4 ASJ AF: 0.0176

Gnomad4 EAS AF: 0.00173

Gnomad4 SAS AF: 0.0317

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.00916

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.00870 Hom.: 2

Bravo AF: 0.0104

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Alpha-methylacyl-CoA racemase deficiency Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	2.2
Dann	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs116206502; hg19: chr5-33987394;