chr5-33994838-G-C

Variant names:

• chr5-33994838-G-C
• rs840409
• NM_014324.6:c.739+3803C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014324.6(AMACR):​c.739+3803C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0909 in 152,132 control chromosomes in the GnomAD database, including 697 homozygotes. 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: 𝑓 0.091 (697 hom., cov: 32)
• Consequence: AMACR NM_014324.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMACR	NM_014324.6	MANE Select	c.739+3803C>G		intron	N/A	NP_055139.4
	AMACR	NM_001167595.2		c.739+3803C>G		intron	N/A	NP_001161067.1
	AMACR	NM_203382.3		c.578+3803C>G		intron	N/A	NP_976316.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMACR	ENST00000335606.11	TSL:1 MANE Select	c.739+3803C>G		intron	N/A	ENSP00000334424.6
	AMACR	ENST00000382085.7	TSL:1	c.739+3803C>G		intron	N/A	ENSP00000371517.3
	AMACR	ENST00000382072.6	TSL:1	c.578+3803C>G		intron	N/A	ENSP00000371504.2

Frequencies

GnomAD3 genomes AF: 0.0910 AC: 13830 AN: 152014 Hom.: 696 Cov.: 32

Gnomad AFR AF: 0.0585

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0616

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0928

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0909 AC: 13836 AN: 152132 Hom.: 697 Cov.: 32 AF XY: 0.0922 AC XY: 6856 AN XY: 74352

African (AFR) AF: 0.0587 AC: 2437 AN: 41512

American (AMR) AF: 0.0615 AC: 940 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 523 AN: 3468

East Asian (EAS) AF: 0.175 AC: 905 AN: 5166

South Asian (SAS) AF: 0.135 AC: 650 AN: 4814

European-Finnish (FIN) AF: 0.104 AC: 1105 AN: 10588

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6946 AN: 67980

Other (OTH) AF: 0.0909 AC: 192 AN: 2112

Alfa AF: 0.0938 Hom.: 89

Bravo AF: 0.0865

Asia WGS AF: 0.133 AC: 463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.9
DANN	Benign	0.38
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs840409; hg19: chr5-33994943;