Variant chr5-33994077-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000335606.11(AMACR):c.739+4564A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0592 in 455,968 control chromosomes in the GnomAD database, including 1,888 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 0.051 ( 368 hom., cov: 32)

Exomes 𝑓: 0.063 ( 1520 hom. )

Consequence

AMACR
ENST00000335606.11 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.247

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
AMACR	NM_014324.6 linkuse as main transcript	c.739+4564A>G	intron_variant	ENST00000335606.11	NP_055139.4
C1QTNF3-AMACR	NR_037951.1 linkuse as main transcript	n.1095+4564A>G	intron_variant, non_coding_transcript_variant
AMACR	NM_001167595.2 linkuse as main transcript	c.739+4564A>G	intron_variant		NP_001161067.1
AMACR	NM_203382.3 linkuse as main transcript	c.578+4564A>G	intron_variant		NP_976316.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMACR	ENST00000335606.11 linkuse as main transcript	c.739+4564A>G		intron_variant		1	NM_014324.6	ENSP00000334424	P1	Q9UHK6-1

Frequencies

GnomAD3 genomes

AF:

0.0507

AC:

7709

AN:

152144

Hom.:

360

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0809

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0367

Gnomad ASJ

AF:

0.0156

Gnomad EAS

AF:

0.152

Gnomad SAS

AF:

0.218

Gnomad FIN

AF:

0.0295

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0216

Gnomad OTH

AF:

0.0545

GnomAD3 exomes

AF:

0.0687

AC:

8814

AN:

128204

Hom.:

669

AF XY:

0.0763

AC XY:

5356

AN XY:

70226

show subpopulations

Gnomad AFR exome

AF:

0.0736

Gnomad AMR exome

AF:

0.0369

Gnomad ASJ exome

AF:

0.0172

Gnomad EAS exome

AF:

0.159

Gnomad SAS exome

AF:

0.198

Gnomad FIN exome

AF:

0.0275

Gnomad NFE exome

AF:

0.0199

Gnomad OTH exome

AF:

0.0376

GnomAD4 exome

AF:

0.0635

AC:

19283

AN:

303706

Hom.:

1520

Cov.:

AF XY:

0.0758

AC XY:

13109

AN XY:

172916

show subpopulations

Gnomad4 AFR exome

AF:

0.0764

Gnomad4 AMR exome

AF:

0.0368

Gnomad4 ASJ exome

AF:

0.0180

Gnomad4 EAS exome

AF:

0.150

Gnomad4 SAS exome

AF:

0.193

Gnomad4 FIN exome

AF:

0.0256

Gnomad4 NFE exome

AF:

0.0215

Gnomad4 OTH exome

AF:

0.0503

GnomAD4 genome

AF:

0.0508

AC:

7732

AN:

152262

Hom.:

368

Cov.:

AF XY:

0.0546

AC XY:

4065

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0808

Gnomad4 AMR

AF:

0.0373

Gnomad4 ASJ

AF:

0.0156

Gnomad4 EAS

AF:

0.152

Gnomad4 SAS

AF:

0.218

Gnomad4 FIN

AF:

0.0295

Gnomad4 NFE

AF:

0.0216

Gnomad4 OTH

AF:

0.0587

Alfa

AF:

0.0321

Hom.:

Bravo

AF:

0.0487

Asia WGS

AF:

0.219

AC:

759

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Pathogenic

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.58

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.37

Position offset: 43

DS_DG_spliceai

0.58

Position offset: 1

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over