Variant chr5-33987949-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014324.6(AMACR):c.*1144A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.03 in 169,432 control chromosomes in the GnomAD database, including 239 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 206 hom., cov: 33)

Exomes 𝑓: 0.037 ( 33 hom. )

Consequence

AMACR
NM_014324.6 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.402

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 links:

C1QTNF3-AMACR (HGNC:):

C1QTNF3-AMACR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 5-33987949-T-C is Benign according to our data. Variant chr5-33987949-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 353237.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
AMACR	NM_014324.6 linkuse as main transcript	c.*1144A>G	3_prime_UTR_variant	5/5	ENST00000335606.11	NP_055139.4
C1QTNF3-AMACR	NR_037951.1 linkuse as main transcript	n.2649A>G	non_coding_transcript_exon_variant	9/9
AMACR	NM_001167595.2 linkuse as main transcript	c.*359A>G	3_prime_UTR_variant	6/6		NP_001161067.1
AMACR	NM_203382.3 linkuse as main transcript	c.*1535A>G	3_prime_UTR_variant	4/4		NP_976316.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMACR	ENST00000335606.11 linkuse as main transcript	c.*1144A>G		3_prime_UTR_variant	5/5	1	NM_014324.6	ENSP00000334424	P1	Q9UHK6-1
AMACR	ENST00000382072.6 linkuse as main transcript	c.*1535A>G		3_prime_UTR_variant	4/4	1		ENSP00000371504		Q9UHK6-4

Frequencies

GnomAD3 genomes

AF:

0.0292

AC:

4437

AN:

152190

Hom.:

199

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00644

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0863

Gnomad ASJ

AF:

0.0164

Gnomad EAS

AF:

0.164

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.00320

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0186

Gnomad OTH

AF:

0.0559

GnomAD4 exome

AF:

0.0368

AC:

630

AN:

17126

Hom.:

Cov.:

AF XY:

0.0349

AC XY:

301

AN XY:

8616

show subpopulations

Gnomad4 AFR exome

AF:

0.00435

Gnomad4 AMR exome

AF:

0.136

Gnomad4 ASJ exome

AF:

0.0227

Gnomad4 EAS exome

AF:

0.179

Gnomad4 SAS exome

AF:

0.129

Gnomad4 FIN exome

AF:

0.00502

Gnomad4 NFE exome

AF:

0.0206

Gnomad4 OTH exome

AF:

0.0477

GnomAD4 genome

AF:

0.0292

AC:

4449

AN:

152306

Hom.:

206

Cov.:

AF XY:

0.0314

AC XY:

2342

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00645

Gnomad4 AMR

AF:

0.0872

Gnomad4 ASJ

AF:

0.0164

Gnomad4 EAS

AF:

0.164

Gnomad4 SAS

AF:

0.106

Gnomad4 FIN

AF:

0.00320

Gnomad4 NFE

AF:

0.0186

Gnomad4 OTH

AF:

0.0558

Alfa

AF:

0.0291

Hom.:

149

Bravo

AF:

0.0370

Asia WGS

AF:

0.113

AC:

393

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Oculocutaneous albinism

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Alpha-methylacyl-CoA racemase deficiency

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.79

DANN

Benign

0.35

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over