5-33988061-C-T

Variant names:

• chr5-33988061-C-T
• rs550891172
• NM_014324.6:c.*1032G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014324.6(AMACR):​c.*1032G>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 0.00000455 in 219,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000045 (0 hom.)
• Consequence: AMACR NM_014324.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500
• Publications: 0 publications found

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:49198): (C1QTNF3-AMACR readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring C1q and tumor necrosis factor related protein 3 (C1QTNF3) and alpha-methylacyl-CoA racemase (AMACR) genes on chromosome 5. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus not likely to produce a protein product. [provided by RefSeq, Mar 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014324.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMACR	NM_014324.6	MANE Select	c.*1032G>A		3_prime_UTR	Exon 5 of 5	NP_055139.4
	AMACR	NM_001167595.2		c.*247G>A		3_prime_UTR	Exon 6 of 6	NP_001161067.1	Q9UHK6-5
	AMACR	NM_203382.3		c.*1423G>A		3_prime_UTR	Exon 4 of 4	NP_976316.1	Q9UHK6-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMACR	ENST00000335606.11	TSL:1 MANE Select	c.*1032G>A		3_prime_UTR	Exon 5 of 5	ENSP00000334424.6	Q9UHK6-1
	AMACR	ENST00000382072.6	TSL:1	c.*1423G>A		3_prime_UTR	Exon 4 of 4	ENSP00000371504.2	Q9UHK6-4
	C1QTNF3-AMACR	ENST00000382079.3	TSL:2	n.*1607G>A		non_coding_transcript_exon	Exon 9 of 9	ENSP00000371511.3	E9PGA6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000455 AC: 1 AN: 219836 Hom.: 0 Cov.: 0 AF XY: 0.00000885 AC XY: 1 AN XY: 112958

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 7634

American (AMR) AF: 0.00 AC: 0 AN: 9200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7948

East Asian (EAS) AF: 0.00 AC: 0 AN: 19116

South Asian (SAS) AF: 0.00 AC: 0 AN: 9326

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13748

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1114

European-Non Finnish (NFE) AF: 0.00000726 AC: 1 AN: 137684

Other (OTH) AF: 0.00 AC: 0 AN: 14066

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.53
PhyloP100		-0.0050

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

Other links and lift over

dbSNP: rs550891172; hg19: chr5-33988166;