rs840409

chr5-33994838-G-C

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMACR	NM_014324.6	c.739+3803C>G		intron_variant		ENST00000335606.11
C1QTNF3-AMACR	NR_037951.1	n.1095+3803C>G		intron_variant, non_coding_transcript_variant
AMACR	NM_001167595.2	c.739+3803C>G		intron_variant
AMACR	NM_203382.3	c.578+3803C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMACR	ENST00000335606.11	c.739+3803C>G		intron_variant		1	NM_014324.6	P1

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

Gnomad4 AFR AF: 0.0587

Gnomad4 AMR AF: 0.0615

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.0909

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.9
Dann	Benign	0.38

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: rs840409; hg19: chr5-33994943;