5-33988130-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.*963C>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 0.0157 in 560,132 control chromosomes in the GnomAD database, including 625 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.043 (472 hom., cov: 32)
  • Exomes 𝑓: 0.0055 (153 hom.)
• Consequence: AMACR NM_014324.6 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.928

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=-0.97).
• BP6: Variant 5-33988130-G-A is Benign according to our data. Variant chr5-33988130-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 353241.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMACR	NM_014324.6	c.*963C>T		3_prime_UTR_variant	5/5	ENST00000335606.11
C1QTNF3-AMACR	NR_037951.1	n.2468C>T		non_coding_transcript_exon_variant	9/9
AMACR	NM_001167595.2	c.*178C>T		3_prime_UTR_variant	6/6
AMACR	NM_203382.3	c.*1354C>T		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMACR	ENST00000335606.11	c.*963C>T		3_prime_UTR_variant	5/5	1	NM_014324.6	P1
AMACR	ENST00000382072.6	c.*1354C>T		3_prime_UTR_variant	4/4	1
AMACR	ENST00000514195.1	n.2006C>T		non_coding_transcript_exon_variant	5/5	1
AMACR	ENST00000506639.5	c.*1434C>T		3_prime_UTR_variant, NMD_transcript_variant	5/5	1

Frequencies

GnomAD3 genomes AF: 0.0430 AC: 6547 AN: 152156 Hom.: 473 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0349

GnomAD4 exome AF: 0.00547 AC: 2231 AN: 407858 Hom.: 153 Cov.: 5 AF XY: 0.00461 AC XY: 982 AN XY: 212884

Gnomad4 AFR exome AF: 0.145

Gnomad4 AMR exome AF: 0.00874

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000280

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000243

Gnomad4 OTH exome AF: 0.0110

GnomAD4 genome AF: 0.0431 AC: 6565 AN: 152274 Hom.: 472 Cov.: 32 AF XY: 0.0408 AC XY: 3041 AN XY: 74462

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.0143

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.0345

Alfa AF: 0.0125 Hom.: 122

Bravo AF: 0.0485

Asia WGS AF: 0.00722 AC: 27 AN: 3478

ClinVar

Significance: Benign/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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 20, 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	-0.97
Cadd	Benign	0.26
Dann	Benign	0.40

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: rs6898962; hg19: chr5-33988235;