dbSNP rs13289: AMACR:c.*2789G>C (chr5-33986304-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014324.6(AMACR):c.*2789G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 152,110 control chromosomes in the GnomAD database, including 21,944 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 0.52 ( 21943 hom., cov: 33)

Exomes 𝑓: 0.50 ( 1 hom. )

Consequence

AMACR
NM_014324.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0710

Publications

18 publications found

Variant links:

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]

AMACR Gene-Disease associations (from GenCC):

alpha-methylacyl-CoA racemase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, G2P
congenital bile acid synthesis defect 4
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

AMACR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMACR	NM_014324.6 link	c.*2789G>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000335606.11	NP_055139.4	Q9UHK6-1
AMACR	NM_203382.3 link	c.*3180G>C		3_prime_UTR_variant	Exon 4 of 4		NP_976316.1	Q9UHK6-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMACR	ENST00000335606.11 link	c.*2789G>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_014324.6	ENSP00000334424.6		Q9UHK6-1

Frequencies

GnomAD3 genomes

AF:

0.519

AC:

78813

AN:

151982

Hom.:

21939

Cov.:

show subpopulations

Gnomad AFR

AF:

0.323

Gnomad AMI

AF:

0.590

Gnomad AMR

AF:

0.521

Gnomad ASJ

AF:

0.582

Gnomad EAS

AF:

0.667

Gnomad SAS

AF:

0.286

Gnomad FIN

AF:

0.652

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.619

Gnomad OTH

AF:

0.510

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.750

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.518

AC:

78832

AN:

152102

Hom.:

21943

Cov.:

AF XY:

0.516

AC XY:

38335

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.322

AC:

13367

AN:

41482

American (AMR)

AF:

0.521

AC:

7970

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.582

AC:

2019

AN:

3472

East Asian (EAS)

AF:

0.667

AC:

3452

AN:

5174

South Asian (SAS)

AF:

0.286

AC:

1380

AN:

4826

European-Finnish (FIN)

AF:

0.652

AC:

6878

AN:

10552

Middle Eastern (MID)

AF:

0.344

AC:

101

AN:

294

European-Non Finnish (NFE)

AF:

0.619

AC:

42051

AN:

67984

Other (OTH)

AF:

0.509

AC:

1077

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1826

3652

5478

7304

9130

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

674

1348

2022

2696

3370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.435

Hom.:

1312

Bravo

AF:

0.509

Asia WGS

AF:

0.435

AC:

1513

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.92

(source)

DANN

Benign

0.55

PhyloP100

0.071

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over