5-33987949-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014324.6(AMACR):c.*1144A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.03 in 169,432 control chromosomes in the GnomAD database, including 239 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (206 hom., cov: 33)
  • Exomes 𝑓: 0.037 (33 hom.)
• Consequence: AMACR NM_014324.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.402

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=-0.94).
• BP6: Variant 5-33987949-T-C is Benign according to our data. Variant chr5-33987949-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 353237.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMACR	NM_014324.6	c.*1144A>G		3_prime_UTR_variant	5/5	ENST00000335606.11
C1QTNF3-AMACR	NR_037951.1	n.2649A>G		non_coding_transcript_exon_variant	9/9
AMACR	NM_001167595.2	c.*359A>G		3_prime_UTR_variant	6/6
AMACR	NM_203382.3	c.*1535A>G		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMACR	ENST00000335606.11	c.*1144A>G		3_prime_UTR_variant	5/5	1	NM_014324.6	P1
AMACR	ENST00000382072.6	c.*1535A>G		3_prime_UTR_variant	4/4	1

Frequencies

GnomAD3 genomes AF: 0.0292 AC: 4437 AN: 152190 Hom.: 199 Cov.: 33

Gnomad AFR AF: 0.00644

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0863

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.00320

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0186

Gnomad OTH AF: 0.0559

GnomAD4 exome AF: 0.0368 AC: 630 AN: 17126 Hom.: 33 Cov.: 0 AF XY: 0.0349 AC XY: 301 AN XY: 8616

Gnomad4 AFR exome AF: 0.00435

Gnomad4 AMR exome AF: 0.136

Gnomad4 ASJ exome AF: 0.0227

Gnomad4 EAS exome AF: 0.179

Gnomad4 SAS exome AF: 0.129

Gnomad4 FIN exome AF: 0.00502

Gnomad4 NFE exome AF: 0.0206

Gnomad4 OTH exome AF: 0.0477

GnomAD4 genome AF: 0.0292 AC: 4449 AN: 152306 Hom.: 206 Cov.: 33 AF XY: 0.0314 AC XY: 2342 AN XY: 74482

Gnomad4 AFR AF: 0.00645

Gnomad4 AMR AF: 0.0872

Gnomad4 ASJ AF: 0.0164

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.00320

Gnomad4 NFE AF: 0.0186

Gnomad4 OTH AF: 0.0558

Alfa AF: 0.0291 Hom.: 149

Bravo AF: 0.0370

Asia WGS AF: 0.113 AC: 393 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Oculocutaneous albinism Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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	-0.94
Cadd	Benign	0.79
Dann	Benign	0.35

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: rs840380; hg19: chr5-33988054;