NM_014324.6:c.*1804G>T

Variant names:

• chr5-33987289-C-A
• rs116206502
• NM_014324.6:c.*1804G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_014324.6(AMACR):​c.*1804G>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 0.00955 in 152,494 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0095 (11 hom., cov: 33)
  • Exomes 𝑓: 0.014 (0 hom.)
• Consequence: AMACR NM_014324.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0140
• Publications: 1 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 5-33987289-C-A is Benign according to our data. Variant chr5-33987289-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 353228.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00955 (1454/152272) while in subpopulation SAS AF = 0.0317 (153/4824). AF 95% confidence interval is 0.0276. There are 11 homozygotes in GnomAd4. There are 740 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

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.*1804G>T		3_prime_UTR	Exon 5 of 5	NP_055139.4
	AMACR	NM_001167595.2		c.*1019G>T		3_prime_UTR	Exon 6 of 6	NP_001161067.1	Q9UHK6-5
	AMACR	NM_203382.3		c.*2195G>T		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.*1804G>T		3_prime_UTR	Exon 5 of 5	ENSP00000334424.6	Q9UHK6-1
	AMACR	ENST00000382072.6	TSL:1	c.*2195G>T		3_prime_UTR	Exon 4 of 4	ENSP00000371504.2	Q9UHK6-4
	C1QTNF3-AMACR	ENST00000382079.3	TSL:2	n.*2379G>T		non_coding_transcript_exon	Exon 9 of 9	ENSP00000371511.3	E9PGA6

Frequencies

GnomAD3 genomes AF: 0.00959 AC: 1459 AN: 152154 Hom.: 12 Cov.: 33

Gnomad AFR AF: 0.00630

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0185

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0321

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.00919

Gnomad OTH AF: 0.0163

GnomAD4 exome AF: 0.0135 AC: 3 AN: 222 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 116

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.0146 AC: 3 AN: 206

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 12

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.00955 AC: 1454 AN: 152272 Hom.: 11 Cov.: 33 AF XY: 0.00994 AC XY: 740 AN XY: 74454

African (AFR) AF: 0.00628 AC: 261 AN: 41546

American (AMR) AF: 0.0185 AC: 283 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0176 AC: 61 AN: 3470

East Asian (EAS) AF: 0.00173 AC: 9 AN: 5188

South Asian (SAS) AF: 0.0317 AC: 153 AN: 4824

European-Finnish (FIN) AF: 0.000659 AC: 7 AN: 10616

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.00916 AC: 623 AN: 68026

Other (OTH) AF: 0.0161 AC: 34 AN: 2112

Alfa AF: 0.00831 Hom.: 4

Bravo AF: 0.0104

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Alpha-methylacyl-CoA racemase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.2
DANN	Benign	0.42
PhyloP100		0.014
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs116206502; hg19: chr5-33987394;