5-33988111-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014324.6(AMACR):c.*982C>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 0.0204 in 516,880 control chromosomes in the GnomAD database, including 612 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (99 hom., cov: 32)
  • Exomes 𝑓: 0.023 (513 hom.)
• Consequence: AMACR NM_014324.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0890

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 5-33988111-G-A is Benign according to our data. Variant chr5-33988111-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 353239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMACR	NM_014324.6	c.*982C>T		3_prime_UTR_variant	5/5	ENST00000335606.11
C1QTNF3-AMACR	NR_037951.1	n.2487C>T		non_coding_transcript_exon_variant	9/9
AMACR	NM_001167595.2	c.*197C>T		3_prime_UTR_variant	6/6
AMACR	NM_203382.3	c.*1373C>T		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMACR	ENST00000335606.11	c.*982C>T		3_prime_UTR_variant	5/5	1	NM_014324.6	P1
AMACR	ENST00000382072.6	c.*1373C>T		3_prime_UTR_variant	4/4	1
AMACR	ENST00000514195.1	n.2025C>T		non_coding_transcript_exon_variant	5/5	1
AMACR	ENST00000506639.5	c.*1453C>T		3_prime_UTR_variant, NMD_transcript_variant	5/5	1

Frequencies

GnomAD3 genomes AF: 0.0152 AC: 2313 AN: 152146 Hom.: 98 Cov.: 32

Gnomad AFR AF: 0.00386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0384

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.0521

Gnomad FIN AF: 0.0171

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00342

Gnomad OTH AF: 0.0153

GnomAD4 exome AF: 0.0226 AC: 8239 AN: 364616 Hom.: 513 Cov.: 4 AF XY: 0.0233 AC XY: 4420 AN XY: 189476

Gnomad4 AFR exome AF: 0.00449

Gnomad4 AMR exome AF: 0.0531

Gnomad4 ASJ exome AF: 0.00285

Gnomad4 EAS exome AF: 0.161

Gnomad4 SAS exome AF: 0.0492

Gnomad4 FIN exome AF: 0.0141

Gnomad4 NFE exome AF: 0.00315

Gnomad4 OTH exome AF: 0.0216

GnomAD4 genome AF: 0.0152 AC: 2317 AN: 152264 Hom.: 99 Cov.: 32 AF XY: 0.0173 AC XY: 1287 AN XY: 74452

Gnomad4 AFR AF: 0.00385

Gnomad4 AMR AF: 0.0387

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.0519

Gnomad4 FIN AF: 0.0171

Gnomad4 NFE AF: 0.00343

Gnomad4 OTH AF: 0.0180

Alfa AF: 0.00864 Hom.: 41

Bravo AF: 0.0169

Asia WGS AF: 0.103 AC: 357 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Oculocutaneous albinism Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 2019

- -

Alpha-methylacyl-CoA racemase deficiency Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.7
Dann	Benign	0.46

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: rs16892066; hg19: chr5-33988216;