5-33988117-C-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_014324.6(AMACR):c.*976G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00989 in 526,660 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0085 ( 10 hom., cov: 33)
Exomes 𝑓: 0.010 ( 46 hom. )
Consequence
AMACR
NM_014324.6 3_prime_UTR
NM_014324.6 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.00900
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.98).
BP6
?
Variant 5-33988117-C-T is Benign according to our data. Variant chr5-33988117-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 353240.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00852 (1297/152302) while in subpopulation SAS AF= 0.0313 (151/4826). AF 95% confidence interval is 0.0272. There are 10 homozygotes in gnomad4. There are 662 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 11 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AMACR | NM_014324.6 | c.*976G>A | 3_prime_UTR_variant | 5/5 | ENST00000335606.11 | ||
C1QTNF3-AMACR | NR_037951.1 | n.2481G>A | non_coding_transcript_exon_variant | 9/9 | |||
AMACR | NM_001167595.2 | c.*191G>A | 3_prime_UTR_variant | 6/6 | |||
AMACR | NM_203382.3 | c.*1367G>A | 3_prime_UTR_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AMACR | ENST00000335606.11 | c.*976G>A | 3_prime_UTR_variant | 5/5 | 1 | NM_014324.6 | P1 | ||
AMACR | ENST00000382072.6 | c.*1367G>A | 3_prime_UTR_variant | 4/4 | 1 | ||||
AMACR | ENST00000514195.1 | n.2019G>A | non_coding_transcript_exon_variant | 5/5 | 1 | ||||
AMACR | ENST00000506639.5 | c.*1447G>A | 3_prime_UTR_variant, NMD_transcript_variant | 5/5 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00854 AC: 1299AN: 152184Hom.: 11 Cov.: 33
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GnomAD4 exome AF: 0.0104 AC: 3911AN: 374358Hom.: 46 Cov.: 4 AF XY: 0.0112 AC XY: 2174AN XY: 194648
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GnomAD4 genome ? AF: 0.00852 AC: 1297AN: 152302Hom.: 10 Cov.: 33 AF XY: 0.00889 AC XY: 662AN XY: 74486
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
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 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at